Teses / dissertações: "Structure du chromosome"

1

Patra, Gurudatt. "Structure of mitotic chromosome and the role of condensin protein in the structural organization of chromosomes". Electronic Thesis or Diss., Strasbourg, 2024. http://www.theses.fr/2024STRAJ020.

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Au cours de la mitose, la chromatine interphasique subit une compaction massive en structures en forme de bâtonnets. Les condensines sont des complexes protéiques dont on sait qu'ils jouent un rôle majeur dans l'organisation des chromosomes mitotiques. Les eucaryotes possèdent deux complexes de condensines conservés, à savoir les condensines 1 et 2. Des études in vitro sur des modèles d'ADN nus montrent que les condensines ont une activité d'extrusion de boucles dans l'organisation des chromosomes. Cependant, il reste encore beaucoup à explorer en ce qui concerne l'étude de la fonction des condensines dans l'environnement encombré de la chromatine. Nous avons utilisé la technologie halo tag où le domaine SMC2 des condensines est marqué par fluorescence à l'aide d'un ligand halo TMR. Cette approche nous aide à localiser les régions riches en condensines dans les chromosomes mitotiques partiellement décondensés en utilisant la cryo-microscopie en lumière à l'intérieur des chromosomes vitrifiés pour les études de cryo-tomographie électronique. Nos tomographies montrent les complexes de condensine dans l'environnement chromatinien. Cela ouvre une fenêtre sur l'étude de l'activité de liaison à l'ADN de la condensine, l'oligomérisation ou le regroupement de la condensine et son interaction avec d'autres composants non histoniques des chromosomes mitotiques
During mitosis, the interphase chromatin undergoes a massive round of compaction into rod-shaped structures. Condensins are protein complexes that have been known to play a major role in mitotic chromosome organization. Eukaryotes have two conserved condensin complexes, namely condensin 1 and 2. In vitro studies on naked DNA templates show evidence for loop extrusion activity of condensins in chromosome organization. However, there is still a lot to explore regarding the study of condensin function inside the crowded chromatin environment. We have used halo tag technology where the SMC2 domain of condensins is tagged to fluorescently label using a halo TMR ligand. This approach helps us to locate condensin-rich regions in partially decondensed mitotic chromosomes using cryo-light microscopy inside the vitrified chromosomes for cryo-electron tomography studies. Our tomograms show condensin complexes inside the chromatin environment. This opens up a window into the study of DNA binding activity of condensin, the oligomerization or clustering of condensin and its interaction with other non-histone components of mitotic chromosomes

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2

Stear, Jeffrey Hamilton. "Studies of chromosome structure and movement in C. elegans /". Thesis, Connect to this title online; UW restricted, 2003. http://hdl.handle.net/1773/5056.

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3

Francki, Michael G. "The midget chromosome as a model to study cereal chromosome structure /". Title page, contents and summary only, 1995. http://web4.library.adelaide.edu.au/theses/09PH/09phf823.pdf.

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4

Woodward, Jessica Christina. "Cell-lineage-specific chromosomal instability in condensin II mutant mice". Thesis, University of Edinburgh, 2016. http://hdl.handle.net/1842/22921.

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In order to equally segregate their genetic material into daughter cells during mitosis, it is essential that chromosomes undergo major restructuring to facilitate compaction. However, the process of transforming diffuse, entangled interphase chromatin into discrete, highly organised chromosomal structures is extremely complex, and currently not completely understood. The complexes involved in chromatin compaction and sister chromatid decatenation in preparation for mitosis include condensins I and II. Mutations in condensin subunits have been identified in human tumours, reflecting the importance of accurate cell division in the prevention of aneuploidy and tumour formation. Most mutations described in TCGA (The Cancer Genome Atlas) and COSMIC (Catalogue of Somatic Mutations in Cancer) are missense, and therefore likely to only partially affect condensin function. Most functional genetic studies of condensin, however, have used loss of function systems, which typically cause severe chromosome segregation defects and cell death. Mice carrying global hypomorphic mutations within the kleisin subunit of the condensin II complex develop T cell lymphomas. The Caph2nes/nes mouse model is therefore a good system for understanding how condensin dysfunction can influence tumourigenesis. However, little is known about which cellular processes are affected in mutant cells before transformation. I therefore set out to use the Caph2nes/nes mouse model to study the consequences of the condensin II deficiency on cell cycle regulation in several different hematopoietic lineages. The Caph2nes/nes mice are viable and fertile, with no obvious abnormalities other than the thymus, which is drastically reduced in size. Previous studies reported greater than a hundred-fold reduction in the number of CD4+ CD8+ thymocytes. I set out to understand why the alteration of a ubiquitously expressed protein which functions in a fundamental cellular process would result in such a cell-type specific block in development. To achieve this, I investigated the possibility that condensin II is involved in interphase processes as well as in mitosis. In addition, I studied the aspects of T cell development that may make this lineage particularly vulnerable to condensin II deficiency. Finally, I carried out a preliminary investigation into the biochemical properties of the condensin complexes. During my PhD., I found strong evidence to suggest that the Caph2nes/nes T cell-specific phenotype arises due to abnormal cell division. However, I was unable to find any evidence to support the hypothesis that the phenotype is a consequence of abnormal interphase processes. Upon systematic analysis of several stages of hematopoietic differentiation, I found that at a specific stage of T cell development, the mutation results in an increased proportion of cells with abnormal ploidy, followed by a drastic reduction in cell numbers. Erythroid cells revealed a similar increase in the frequency of hyperdiploid cells, but no reduction in cell numbers. B cells and hematopoietic precursors did not reveal an increase in hyperdiploidy, or a reduction in cell numbers in wildtype relative to mutant. Subsequently, I found preliminary evidence to suggest that the T cell-specificity may be due to more rapid progression of CD4+ CD8+ T cells from S phase to M phase, relative to other hematopoietic stages. Finally, a preliminary investigation into the biochemical properties of the condensin complex revealed apparent imbalances in the expression of condensin subunits in T, B and erythroid cells. The sedimentation profile of CAP-H2 from whole-thymus extract did not exclude the possibility that condensin subunits might be forming heavier-weight complexes with non-SMC proteins. Further work must be carried out to determine whether this sedimentation pattern is unique to T cells.

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5

Dadon, Daniel Benjamin. "3D chromosome structure and chromatin proteomics". Thesis, Massachusetts Institute of Technology, 2016. http://hdl.handle.net/1721.1/104174.

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Thesis: Ph. D., Massachusetts Institute of Technology, Department of Biology, 2016.
Cataloged from PDF version of thesis. "May 2016."
Includes bibliographical references.
The selective interpretation of the genome through transcription enables the production of every cell type's distinct gene expression program from a common genome. Transcription takes place within, and is controlled by, highly organized three-dimensional (3D) chromosome structures. The first part of the work presented here describes the generation of 3D chromosome regulatory landscape maps of human naive and primed embryonic stem cells. To create these 3D chromosome regulatory landscape maps, genome-wide enhancer and insulator locations were mapped and then placed into a 3D interaction framework formed by cohesin-mediated 3D chromosome structures. Enhancer (H3K27ac) and insulator (CTCF) locations were mapped using ChIP-sequencing, whereas 3D chromosome structures were detected by cohesin-ChIA-PET. 3D chromosome structures connecting insulators (CTCF-CTCF loops) were shown to form topologically associating domains (TADs) and insulated neighborhoods, which were mostly preserved in the transition between naive and primed states. Insulated neighborhoods are critical for proper gene expression, and their disruption leads to the improper regulation of local gene expression. Changes in enhancer-promoter loops occurred within preserved insulated neighborhoods during cell state transition. The CTCF anchors of CTCF-CTCF loops are conserved across species and are frequently mutated in cancer cells. These 3D chromosome regulatory landscapes provide a foundation for the future investigation of the relationship between chromosome structure and gene control in human development and disease. The work presented in the second part focuses on developing an approach called "chromatin proteomic profiling" to identify protein factors associated with various active and repressed portions of the genome marked by specific histone modifications. The histone modifications assayed by chromatin proteomic profiling are associated with genomic regions where specific transcriptional activities occur, thus implicating the identified proteins in these activities. This chromatin proteomic profiling study revealed a catalog of known, implicated, and novel proteins associated with these functionally characterized genomic regions.
by Daniel Benjamin Dadon.
Ph. D.

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6

Croft, Jenny Anne. "Correlating mammalian chromosome structure and function". Thesis, University of Edinburgh, 1998. http://hdl.handle.net/1842/13491.

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The euchromatin of mammalian chromosomes is broadly divided into two types with opposing characteristics: G-bands are revealed by Giemsa staining. These bands are generally late replicating, T-rich, low in gene density and appear to have a "closed" chromatin structure. R-bands are revealed by reverse Giemsa staining. These bands are generally early replicating, GC-rich, high in gene density and appear to have a more "open" chromatin structure. These two band types are intercalated throughout the mammalian genome making comparative studies of their behaviour difficult. However, in the human genome, chromosome 18 predominantly displays the features of G-bands and chromosome 19 generally displays the features of R-bands. These chromosomes were shown to be comparable in DNA content and size at metaphase and are, thus, ideal to investigate further the apparent links between chromosome structure and function. Some models of chromosome structure suggest differences in the higher order packaging of the different band types of metaphase chromosomes. Any differences should be reflected in the overall structure of chromosomes 18 and 19. Combining fluorescence in situ hybridisation and biochemical extraction of metaphase chromosomes, I detected no significant differences in their structure. In contrast, the two chromosomes demonstrated different structural characteristics in the interphase nucleus. I found that chromosome 18 occupies a relatively condensed territory, close to the periphery of the nucleus, while chromosome 19 occupies a considerably larger territory, more centrally located. My studies of different cell types and on cells at different stages of the cell cycle suggest that these characteristics generally apply in human cells, but not in a somatic cell hybrid background. Analysis of nuclei with a reciprocal 18:19 translocation showed that the translocated segments were orientated towards the positions occupied by their structurally normal homologues. The size but not the positioning of an interphase territory appears to be dependent on transcriptional activity.

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7

Almuhur, Rana Ahmad Suleiman. "Integrating chromatin structure and global chromosome dynamics". Thesis, University of Birmingham, 2015. http://etheses.bham.ac.uk//id/eprint/5573/.

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DNA associates with proteins to form chromatin which is essential for the compaction of the DNA into the cell nucleus and is highly dynamic in order to allow the different biological processes of the DNA to occur. Chromatin compaction is achieved at different hierarchical levels: the 10nm fibre (DNA associates to nucleosomes formed by different histones), the Higher Order Chromatin fibre and the 300 nm chromosome structures. This study has shown that both H1 and H4 histones play a crucial role in preserving meiotic as well as mitotic chromosome structure and functional genome integrity in Arabidopsis. The role of the different linker histone H1 isoforms as well as the core histone H4 in Arabidopsis thaliana was investigated using T-DNA and RNAi mutant lines which showed different meiotic defects. Chromosomal breaks as well as non-homologous connections in the h4RNAi were linked to 45S/5S rDNA disorganisation, suggesting that H4 preserves chromosome integrity at these rDNA regions. Ath1.1 mutant presented univalents and reduced chiasma frequency at metaphase I, linked to a severe defect in ASY1 localisation on the meiotic chromosome axes. Thus, indicating that histone H1.1 is vital for proper chromatin axis organization that permit normal loading of recombination machinery proteins in Arabidopsis.

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8

Gilbert, Sandra L. (Sandra Leigh) 1968. "Chromatin structure of the inactive X chromosome". Thesis, Massachusetts Institute of Technology, 1999. http://hdl.handle.net/1721.1/85344.

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9

Ross, Brian Christopher. "Computational tools for modeling and measuring chromosome structure". Thesis, Massachusetts Institute of Technology, 2012. http://hdl.handle.net/1721.1/79262.

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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Physics, 2012.
Cataloged from PDF version of thesis.
Includes bibliographical references (p. 99-112).
DNA conformation within cells has many important biological implications, but there are challenges both in modeling DNA due to the need for specialized techniques, and experimentally since tracing out in vivo conformations is currently impossible. This thesis contributes two computational projects to these efforts. The first project is a set of online and offline calculators of conformational statistics using a variety of published and unpublished methods, addressing the current lack of DNA model-building tools intended for general use. The second project is a reconstructive analysis that could enable in vivo mapping of DNA conformation at high resolution with current experimental technology.
by Brian Christopher Ross.
Ph.D.

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10

Horsley, Sharon Wendy. "Characterisation of chromosome 16 rearrangements in patients with alpha thalassaemia". Thesis, Oxford Brookes University, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.325201.

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11

Smith, Helen. "Condensin II Regulation and Function in Polyploid and Female Meiotic Cells in Drosophila melanogaster". Diss., The University of Arizona, 2010. http://hdl.handle.net/10150/194783.

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The cell's nucleus contains DNA in the form of chromosomes, which are the hereditary content of the organism. The proper transmission of DNA from one generation to the next is critical. Along with this crucial process, cells will also need to transcribe the DNA, silence certain genes (or whole chromosomes) during development and regulate other chromosome dynamics that are still being identified. The molecular components responsible for these processes are starting to be identified. However, the regulation of these components and how they interact with each other is not well understood.The condensin complex is one component that has been identified to play a role in chromosome dynamics. Activity of the complex has been studied in vitro but in vivo activity has been difficult to measure. Similarly, understanding the regulation of the complex has been difficult given the lack of assays and that the complex is essential for cell survival. In this dissertation, I have identified and characterized a regulator of condensin II function using Drosophila melanogaster. The chromo-domain protein Mrg15 interacts with condensin II to inhibit homologous chromosome interactions.Lastly, I look at the role of condensin II in female meiosis. Meiosis involves pairing and subsequent segregation of homologous chromosomes. The process of the initial pairing has remained elusive but specialized structures have evolved to maintain this pairing. Condensin II can antagonize a basal level of homologous pairing and also removes the specialized structure that pair meiotic chromosomes. This dissertation will add to the growing knowledge of the regulation of the condensin II complex and its role in female meiosis.

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12

Baudry, Lyam. "Investigating chromosome dynamics through Hi-C assembly". Electronic Thesis or Diss., Sorbonne université, 2019. http://www.theses.fr/2019SORUS026.

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L'avènement des technologies de séquençage ADN à haut-debit a initié une tendance grandissante dans l'assemblage de génomes. La qualité de ces génomes est un prérequis essentiel pour comprendre les interactions au sein de et entre ces chromosomes. Nos méthodes se basent principalement sur les technologies de capture de conformation de chromosomes comme le Hi-C. Lors d'un protocole de Hi-C, les molécules d'ADN sont réticulées avec les protéines environnantes pour former un complexe protéine-ADN statique et volumineux. Ceci permet de capturer la conformation spatiale en piégeant les molécules physiquement proches dans l'espace. Ainsi, le Hi-C est très approprié pour l'analyse de la structure 3D des génomes, ce qui permet d'obtenir un certain nombre d'informations sur le génome. Il a été ainsi montré que sa structure tridimensionnelle peut être reliée directement à sa structure 1D grâce aux propriétés physiques des polymères d'ADN. De plus, une telle proximité en 3D donne également accès à des informations de compartimentation, ce qui a ouvert la voie à une nouvelle approche de binning métagénomique, connue sous le nom de meta3C. Au cours de ce travail, nous étendons ces méthodes à des études de cas présentant une complexité grandissante. Tout d'abord, nous améliorons les outils d'assemblage de génomes et démontrons leur validité avec l'assemblage de Ectocarpus sp., puis nous mettons en évidence des réarrangements chromosomiques au sein d'assemblages joints de Trichoderma reesei et Cataglyphis hispanica. Enfin, nous utilisons la même approche avec le binning métagénomique sur des échantillons de souris in vivo afin de reconstruire des centaines de génomes
The advent of high-throughput DNA sequencing technologies has set off an expanding trend in genome assembling and scaffolding. Such genome quality is an essential preliminary to understand interactions between and among chromosomes. We built upon a computational and technological framework that let us tackle genome assembly problems of increasing complexity. Our methods are mainly based on chromosome conformation capture technologies such as Hi-C. In a Hi-C experiment, DNA molecules are cross-linked with the surrounding proteins and form a large, static protein-DNA complex. This captures the spatial conformation by trapping together molecules that are physically close to each other. Therefore, Hi-C is very suitable for 3D genome structure analysis, which lets us infer a wealth of information about the genome. It was indeed shown that the tridimensional structure of the genome can be unambiguously linked to its 1D structure thanks to the physical properties of DNA polymers. Moreover, such 3D proximity also gives access to cell compartment information, thus opening the way for an additional approach for metagenomic binning, known as meta3C. In this work, we expand upon these methods and apply them to use cases with more and more complexity. We first improve on tools for genome assembly and demonstrate their validity with the scaffolding of Ectocarpus sp., then unveil rearrangements in joint scaffoldings of Trichoderma reesei and Cataglyphis hispanica. Lastly, we use the same approach with metagenomic binning on live mouse microbiome samples to reconstruct hundreds of genomes

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13

Besson, Dorian. "Regulation of cohesin by the TORC1 complex in the yeast Schizosaccharomyces pombe". Electronic Thesis or Diss., Bordeaux, 2024. http://www.theses.fr/2024BORD0166.

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Cohésine est un complexe protéique capable de capturer les molécules d’ADN. Cohésine assure la cohésion des chromatides sœurs, essentielle à la ségrégation des chromosomes lors des divisions nucléaires. Elle intervient également en interphase via la formation de boucles d’ADN intra-chromosomiques qui façonnent l’architecture fonctionnelle du génome. L’expression génique est ainsi régulée par l’organisation spatiale des chromosomes, notamment au cours du développement et de la différenciation. Les nombreuses fonctions de cohésine suggèrent une régulation fine dans le temps et l’espace. Le laboratoire adresse cette question via une approche génétique chez l’organisme modèle Schizosaccharomyces pombe. La capture de l’ADN par cohésine nécessite l’intervention d’un complexe de chargement, Mis4/Ssl3 (hNIPBL/MAU2). Le mutant mis4-G1487D est thermosensible de croissance à 36°C. A température restrictive, il présente un défaut de chargement des cohésines sur les chromosomes et une fréquence élevée de défauts de ségrégation des chromosomes lors de la mitose. Un crible génétique a identifié des mutations extragéniques capables de restaurer la croissance de mis4-G1487D à 36°C. Cinq de ces mutations affectent le gène mip1 et une le gène tor2. Mip1 et Tor2 sont des composants du complexe TORC1, l’équivalent de mTOR (Mammalian Target Of Rapamycin) qui est une kinase régulatrice majeure du métabolisme et de la croissance cellulaire. Son activité est stimulée par des signaux tels que la disponibilité en nutriments, niveaux d’énergie, hormones et facteurs de croissance. Chez S. pombe, Tor2 est la sous-unité catalytique et Mip1 (hRaptor) participe au choix du substrat. Les gènes tor2 et mip1 sont essentiels à la viabilité cellulaire indiquant que les allèles issus du crible sont hypomorphes. Nous avons focalisé nos travaux sur mip1-R401G qui ne provoque quasiment pas de défaut de croissance tout en étant un excellent suppresseur. De façon remarquable, mip1-R401G restaure l’association de cohésine aux chromosomes et diminue la fréquence de ségrégation anormale des chromosomes du mutant mis4-G1487D à 36°C. En fond mis4+, mip1-R401G provoque une augmentation de la quantité de cohésine associée aux chromosomes. Des résultats similaires ont été obtenus en traitant les cellules à la Rapamycine, un inhibiteur de TORC1. Ces données suggèrent que l’activité de TORC1 régule de façon négative le complexe de chargement des cohésines chez S. pombe.Toutes les sous-unités du complexe TORC1 co-purifient avec cohésine et Mis4. La sous unité Psm1 de cohésine et Mis4 sont hypophosphorylées en fond mip1-R401G. La combinaison de mutations imitant l’état non-phosphorylé réduit la fréquence des défauts de ségrégation de mis4-G1487D. Réciproquement les défauts de ségrégation sont exacerbés par les mutations imitant l’état phosphorylé. Ces données indiquent que TORC1 contrôle l’état de phosphorylation de Psm1 et Mis4. La fonction connue de TORC1 étant d’adapter la cellule aux changements environnementaux, nous avons mis en œuvre une analyse du transcriptome dans diverses situations expérimentales (composition du milieu de culture, température, phase du cycle cellulaire). Toutes expériences confondues, 337 gènes sont différentiellement exprimés en fond mis4-G1487D par rapport au contrôle sauvage. De façon remarquable les gènes affectés sont largement différents d’une condition à l’autre, suggérant un défaut de réponse adaptative. D’autre part, la quasi-totalité des gènes dérégulés par mis4-G1487D le sont également par mip1-R401G. Ces gènes sont préférentiellement localisés aux extrémités des chromosomes et sont impliqués dans la réponse au stress et la différenciation sexuelle.L’ensemble des données suggère que cohésine soit un effecteur de la voie TORC1 pour adapter la cellule aux changements environnementaux. Ce mécanisme ferait intervenir un changement de l’expression génique induit par une modification de l’organisation spatiale du génome
Cohesin is a protein complex capable of capturing DNA molecules. Cohesin ensures the cohesion of sister chromatids, which is essential for chromosome segregation during nuclear divisions. It is also involved in interphase via the formation of intra-chromosomal DNA loops that shape the functional architecture of the genome. Gene expression is thus regulated by the spatial organisation of chromosomes, particularly during development and differentiation. The many functions of cohesin suggest fine regulation in time and space. The laboratory is addressing this question using a genetic approach in the model organism Schizosaccharomyces pombe. DNA capture by cohesin requires the intervention of a loading complex, Mis4/Ssl3 (hNIPBL/MAU2). The mis4-G1487D mutant is thermosensitive to growth at 36°C, has a defect in cohesin loading on chromosomes and a high frequency of chromosome segregation defects during mitosis. A genetic screen identified extragenic mutations capable of restoring the growth of mis4-G1487D at 36°C. Five of these mutations affect the mip1 gene and one the tor2 gene. Mip1 and Tor2 are components of the TORC1 complex, the equivalent of mTOR (Mammalian Target Of Rapamycin), which is a major regulatory kinase for cell metabolism and growth. Its activity is stimulated by signals such as the availability of nutrients, energy levels, hormones and growth factors. In S. pombe, Tor2 is the catalytic subunit and Mip1 (hRaptor) is involved in substrate selection. The tor2 and mip1 genes are essential for cell viability, indicating that the alleles produced by the screen are hypomorphic. We focused our work on mip1-R401G, which causes virtually no growth defects while being an excellent suppressor. Remarkably, mip1-R401G restored cohesin association with chromosomes and reduced the frequency of abnormal chromosome segregation in the mis4-G1487D mutant at 36°C. In the mis4+ background, mip1-R401G increased the amount of cohesin associated with chromosomes. Similar results were obtained by treating the cells with Rapamycin, a TORC1 inhibitor. These data suggest that TORC1 activity negatively regulates the cohesin loading complex in S. pombe.All subunits of the TORC1 complex co-purify with cohesin and Mis4. The Psm1 subunit of cohesin and Mis4 are hypophosphorylated in the mip1-R401G background. The combination of mutations mimicking the non-phosphorylated state reduces the frequency of mis4-G1487D segregation defects. Conversely, segregation defects are exacerbated by mutations mimicking the phosphorylated state. These data indicate that TORC1 controls the phosphorylation state of Psm1 and Mis4. Given that TORC1's known function is to adapt the cell to environmental changes, we carried out a transcriptome analysis in various experimental situations (culture medium composition, temperature, cell cycle phase). Taking all experiments together, 337 genes were differentially expressed in the mis4-G1487D background compared with the wild-type control. Remarkably, the genes affected differed widely from one condition to another, suggesting that mis4-G1487D cells have a defective adaptive response. Almost all the genes deregulated by mis4-G1487D were also deregulated by mip1-R401G. These genes are preferentially located at the ends of chromosomes and are involved in the stress response and sexual differentiation.Taken together, the data suggest that cohesin is an effector of the TORC1 pathway for adapting the cell to environmental changes. Mechanistically, this might involve a change in gene expression induced by a modification in the spatial organization of the genome

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14

Riley, Anthony David. "Probing chromosome structure using multidimensional scaling of DNA contact matrices". Thesis, University of Leeds, 2014. http://etheses.whiterose.ac.uk/7262/.

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Chromosome conformation capture technology has provided a route to studying genome structure through DNA-DNA contact-counts. An iteration of chromosome conformation capture technology is Hi-C, which provides genome wide two dimensional contact-count data. The contact-count data from Hi-C can be viewed as a proxy for distance and using some transform function can be transformed into estimated distances. These estimated distances can be fitted into Euclidean space using the statistical tools of multidimensional scaling to give estimated chromosome or genome configurations. The first part of this thesis takes the Hi-C contact-count data for Chromosome 14, transforms it into estimated distances which are fitted into Euclidean space to give an estimated chromosome configuration. Steps are also taken to pre-process the genome contact-count matrix to refine the information held within it. The pre-processed genome contact-count matrix is transformed into estimated distances, which are fitted into Euclidean space to give an estimated genome configuration. The estimated chromosome and genome configurations are investigated, to find if known features of these structures are captured through fitting the Hi-C data. The second part of this thesis simulates contact-count data from simple configurations. Using the inverse of the transform functions the distances between points in a configuration can be transformed into mean contact-counts. The mean contact-counts are perturbed using a suitable distribution function to provide perturbed contact-counts, which are transformed into perturbed distances. The perturbed distances can be fitted into Euclidean space to give a fitted configurations. The properties of the fitted configurations are investigated and compared with the original configurations, and the properties of the perturbed distances are also investigated. Then steps are taken to improve the fitted configurations using information from the properties of the perturbed distances, with the successful techniques applied to estimating the chromosome configuration.

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15

Buitrago, Ospina Diana Camila. "Understanding the link between chromatin structure, chromosome conformation and gene regulation". Doctoral thesis, Universitat de Barcelona, 2019. http://hdl.handle.net/10803/668639.

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Understanding the connection between DNA organization in the nucleus, and cell functioning is one of the most intriguing problems in biology. Although many interdisciplinary efforts have been developed for this aim, the mechanisms of DNA folding in such a large scale are largely unknown. Therefore, the complexity of genome structure requires different techniques to tackle several resolution levels. In this thesis, several scales of genome folding are studied using theoretical methods. First, we focus on the DNA sequence dependent properties which define the propensity of specific loci to be recognized by proteins, finding that the flexibility of specific DNA sequences might explain their prevalence in the genome. DNA sequence dependent properties are also important to define the first layer of chromatin organization: the nucleosome. Physical descriptors of the DNA sequence combined with the propensity for transcription factor binding are highly informative on the location of nucleosome depleted regions, which guide the position of +1 and –last nucleosomes, the rest of nucleosomes in the gene body being placed by statistical phasing. There is a clear correlation between transcriptional activity and nucleosome phasing at gene body, the causal relationship is transcription -> nucleosome organization rather than the opposite A package for the comparative analysis of nucleosome organization was also developed in this thesis to quantitative predict changes in nucleosome organization occurring when perturbations are introduced to the cell. Finally, we studied both the changes at the nucleosome level and at larger scale produced by the induction of DNA methylation on a natively unmethylated genome, developing a Hi-C based 3D model to gain insights into the chromatin rearrangements observed. We found very significant changes in chromatin structure induced by methylation, which are reflected in gene expression and cellular phenotype. Interestingly, these changes are found in a model organism that has not proteins prepared to recognize methylation, and accordingly can be assigned to intrinsic (not protein-mediated) effects of methylation.
Comprender la conexión entre la organización del ADN en el núcleo y el funcionamiento celular es uno de los problemas más interesantes en biología. Aunque se han desarrollado muchos esfuerzos interdisciplinarios para esto, los mecanismos de plegamiento del ADN son en gran medida desconocidos. Por lo tanto, la complejidad de la estructura del genoma requiere diferentes técnicas para abordar varios niveles de resolución. En esta tesis, se estudian varias escalas de plegamiento del genoma utilizando métodos teóricos. Primero, nos centramos en las propiedades dependientes de la secuencia de ADN que definen la propensión de regiones específicas a ser reconocidos por las proteínas, descubriendo que la flexibilidad de ciertas secuencias de ADN podría explicar su prevalencia en el genoma. Las propiedades físicas del ADN también son importantes para definir la primera capa de organización de la cromatina: el nucleosoma. Los descriptores físicos de la secuencia de ADN combinados con la propensión a la unión de factores de transcripción son muy informativos sobre la posición de las regiones no afines a la formación de nucleosomas, que guían la posición de los nucleosomas +1 y –último, y el resto de los nucleosomas en el cuerpo del gen se coloca por posicionamiento estadístico. Adicionalmente, encontramos que existe una clara correlación entre la actividad transcripcional y la fase de nucleosomas en el cuerpo del gen. En esta tesis también se desarrolló un paquete para el análisis comparativo de la organización de nucleosomas que permite identificar cuantitativamente los cambios en el posicionamiento de los nucleosomas que ocurren cuando se introducen perturbaciones en la célula. Finalmente, estudiamos tanto los cambios a nivel de nucleosomas como a mayor escala producidos por la inducción de metilación del ADN en un genoma que originalmente no tiene metilación, desarrollando un modelo 3D basado en Hi-C para estudiar la reorganización de la cromatina. Encontramos cambios muy significativos en la estructura de la cromatina inducidos por la metilación, que se reflejan en la expresión génica y el fenotipo celular, en un organismo modelo que no tiene proteínas que reconocen la metilación y, en consecuencia, pueden deberse a los efectos intrínsecos de la metilación.

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16

Wallace, Julie Ann 1977. "Mitotic regulators and their effects on Drosophila : chromosome structure during development". Thesis, Massachusetts Institute of Technology, 2005. http://hdl.handle.net/1721.1/31187.

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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2005.
Includes bibliographical references.
Variants of the canonical cell cycle are frequently used in nature to accomplish specific developmental goals. In one such variant, the endocycle, synthesis phase alternates with a gap phase without an intervening mitosis, producing cells that have multiple copies of the genome. These cells show diversity in their chromosome structure; at one extreme, the sister chromatids are separate (polyploid) and at the other extreme, the sisters are held together (polytene). The endocycle itself can be modified and these variations are speculated to correlate with the observed differences in chromosome structure. In this thesis, we have analyzed the contribution of mitotic regulators to the endocycle and polytene chromosome structure in Drosophila. We show that morula, a gene required for the transition from polytene to polyploid chromosome structure in Drosophila nurse cells, is a subunit of the anaphase-promoting complex/cyclosome. Increasing levels of cyclin B, a known mitotic target of the APC/C, does not alter the timing of the transition, indicating that CYCLIN B is not the only APC/C target at the polyteny-polyploidy transition. In mitosis, activity of APC/C and POLO lead to the loss of sister-chromatid cohesion and we find that mutants in polo are unable to progress through the polyteny-polyploidy transition. Finally, we find that the cohesin complex, a complex required for the physical attachment of sister chromatids in mitosis, is required for proper polytene chromosome structure in the salivary gland. These results describe a requirement for the cohesin complex in a variant of the cell cycle lacking mitosis and indicate that sister-chromatid cohesion differentiates polytene and polyploid chromosome structures.
by Julie Ann Wallace.
Ph.D.

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17

Cole-Showers, Curtis Lanre. "Population structure and demographics in Nigerian populations utilizing Y-chromosome markers". University of the Western Cape, 2014. http://hdl.handle.net/11394/5326.

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Philosophiae Doctor - PhD
Nigeria is peopled by ethnically and linguistically diverse populations of which little were known until the last few millennial. The absence of major natural geographical barrier increases the possibility of the populations being affected by the same demographic events. The aim of this thesis was to ascertain the genetic variations and demographics in five major Nigerian populations using Y-markers. This was done by determining the genetic structures of the Afro-asiatic speaking Hausa (n=78) of Northern Nigeria and the Niger Congo speaking populations of Igbo (n=119), Yoruba (n=238), Bini (n=13) and Ijaw (n=15) of Southern Nigeria all spread over 22 geographical origins and four (North, South east, south west and South south) geographical regions. They were compared with more than 2000 individuals from 46 populations of 20 other African and Middle Eastern countries, in published literature. The Scientific Working Group on DNA Analysis Methods (SWGDAM) recommended Y-Short Tandem Repeats (STRs) and nine Y-Single Nucleotide Polymorphisms (SNPs) haplogroups were typed with multiplex Polymerase Chain Reaction (PCR), Restriction Fragment Length Polymorphisms (RFLP) and High Resolution Melting (HRM). Summary statistics and measures of diversity were determined. Population structure was assessed with Population Pairwise Differences, hierarchical Analysis of Molecular Variance, Multidimensional scaling and correspondence analysis plots. Mantel’s test was used to assess the correlation of genetic distances with geographic distances. Demographic inferences were assessed with lineage based Network reconstruction, Spatial autocorrelation plots, effective migrants per population and both Inter and Intra-lineages Times to the Most Recent Common Ancestor (TMRCA). The patterns of diversity of the Y-markers showed a North-South gradient and a notable sub-structure among the Hausa populations. The Niger-Congo speakers displayed rare presence of haplogroups R and E1b1b but a preponderance of E1b1a7. Overall, the Y markers showed high diversities and significant genetic sub-structure within the Hausa populations of Nigeria with stronger linguistic than geographical bias. The demographic evaluations gave credence for genetic validation of both historical records and archeological findings among these Nigerian populations. These populations showed stronger affiliations with other sub-Saharan African populations rather than with North African or Middle Eastern populations, lacking evidence for the Middle Eastern origins of the male founders of these populations. Finally, the contribution of these Nigerian dataset would greatly enhance the Africa meta-population on the YHRD with more than 274 new haplotypes of forensic estimation significance.

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18

Bähler, Jürg. "Meiotic chromosome structure, pairing and recombination in fission and budding yeast /". [S.l : s.n.], 1994. http://www.ub.unibe.ch/content/bibliotheken_sammlungen/sondersammlungen/dissen_bestellformular/index_ger.html.

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19

Hemming, D. J. "An immunological study of the role of histones in lampbrush chromosome structure". Thesis, University of Liverpool, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.383516.

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20

Johansson, Anna-Mia. "Chromosome-wide gene regulatory mechanisms in Drosophila melanogaster". Doctoral thesis, Umeå universitet, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet), 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-33928.

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In Drosophila there are two different chromosome-wide targeting systems, the dosage compensation system that equalizes the transcriptional output from X-linked genes between males and females, and the regulation of the 4th chromosome mediated by the POF protein. The best studied of these two mechanisms is the dosage compensation system. To attain dosage compensation in Drosophila at least five different proteins, encoded by the male-specific lethal genes msl1, msl2, msl3, mle and mof, are required. These proteins together with two non-coding RNAs (roX1 and roX2) form a dosage compensation complex (MSL complex), which binds exclusively to the X chromosome in Drosophila males and up-regulates the transcription approximately two times. In this thesis I show that roX1 and roX2 are most likely the only non-coding RNAs within the MSL complex. As expected, the roX transcripts were enriched within the MSL complex. Interestingly, one additional transcript was identified within the MSL complex. This transcript did not associate with the X chromosome and is therefore not believed to be involved in up-regulation of the X-linked genes. This transcript encodes for the rate limiting component in the MSL complex, the MSL2 protein. A model is proposed in which free, partial or complete, MSL complex feed-back regulates the amount of msl2 transcript, and thereby limits the MSL complex production. The second chromosome-wide regulatory system in flies acts on an autosome, the heterochromatic 4th chromosome. This regulation is a balancing mechanism between at least two different proteins, the chromosome 4 specific protein painting of fourth (POF) and heterochromatin protein 1 (HP1). POF binds to nascent RNAs transcribed from the 4th chromosome and HP1 target the same set of genes at the chromatin level. POF stimulates the transcribed genes, while HP1 represses them; together they create the most optimal condition for these genes. This type of balancing mechanism may be a more general way to fine-tune transcription at a chromosome-wide level and raises the question about autosomal gene regulation as a general mechanism.

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21

Cinato, Elisa. "Structure et expression du gène IFNA R2 humain : identification de la deuxième chaîne du récepteur des interférons alpha/bêta". Montpellier 2, 1996. http://www.theses.fr/1996MON20042.

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Seule la premiere chaine du recepteur des ifn-alpha/beta avait ete caracterisee. Nous avons clone le gene ifnar2, qui appartient au groupe de genes de recepteurs des cytokines sur le chromosome 21 humain. Le gene ifnar2 est a l'origine de quatre messagers differents, codant pour trois proteines. Une est secretee, deux sont des proteines transmembranaires, partageant le meme domaine extracellulaire, mais avec queue cytoplasmique differente. Nous avons montre, par complementation dans les cellules humaines mutantes u5, que la proteine avec domaine intracellulaire long est un composant fonctionnel du recepteur des ifn-alpha/beta humain

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22

Newman, Scott. "The structure and evolution of breast cancer genomes". Thesis, University of Cambridge, 2011. https://www.repository.cam.ac.uk/handle/1810/239397.

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Chromosome changes in the haematological malignancies, lymphomas and sarcomas are known to be important events in the evolution of these tumours as they can, for example, form fusion oncogenes or disrupt tumour suppressor genes. The recently described recurrent fusion genes in prostate and lung cancer proved to be iconic examples as they indicated that important gene fusions are found in the common epithelial cancers also. Breast cancers often display extensive structural and numerical chromosome aberration and have among the most complex karyotyes of all cancers. Genome rearrangements are potentially an important source of mutation in breast cancer but little is known about how they might contribute to this disease. My first aim was to carry out a structural survey of breast cancer cell line genomes in order to find genes that were disrupted by chromosome aberrations in 'typical' breast cancers. I investigated three breast cancer cell lines, HCC1187, VP229 and VP267 using data from array painting, SNP6 array CGH, molecular cytogenetics and massively parallel paired end sequencing. I then used these structural genomic maps to predict fusion transcripts and demonstrated expression of five fusion transcripts in HCC1187, three in VP229 and four inVP267. Even though chromosome aberrations disrupt and fuse many genes in individual breast cancers, a major unknown is the relative importance and timing of genome rearrangements compared to sequence-level mutation. For example, chromosome instability might arise early and be essential to tumour suppressor loss and fusion gene formation or be a late event contributing little to cancer development. To address this question, I considered the evolution of these highly rearranged breast cancer karyotypes. The VP229 and VP267 cell lines were derived from the same patient before and after therapy-resistant relapse, so any chromosome aberration found in both cell lines was probably found in the common in vivo ancestor of the two cell lines. A large majority of structural variants detected by massively parallel paired end sequencing, including three fusion transcripts, were found in both cell lines, and therefore, in the common ancestor. This probably means that the bulk of genome rearrangement pre-dated the relapse. For HCC1187, I classified most of its mutations as earlier or later according to whether they occurred before or after a landmark event in the evolution of the genome-endoreduplication (duplication of its entire genome). Genome rearrangements and sequence-level mutations were fairly evenly divided between earlier and later, implying that genetic instability was relatively constant throughout the evolution of the tumour. Surprisingly, the great majority of inactivating mutations and expressed gene fusions happened earlier. The non-random timing of these events suggests many were selected.

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23

Kabir, Sadia. "Molecular analysis of structure of chromosome 6R of triticale T701-4-6 /". Title page, summary and contents only, 1997. http://web4.library.adelaide.edu.au/theses/09PH/09phk108.pdf.

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24

Bland, Michael Jason. "Study of the constraints sustaining the two chromosome genome structure of vibrio cholerae". Paris 6, 2013. http://www.theses.fr/2013PA066794.

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The majority of bacteria have their genome organized into a single circular chromosome. These chromosomes are organized into spatially confined regions, which are characterized by having low contact frequencies between loci in different regions. These regions are formed as a result of processes related to gene transcription, chromosome replication and segregation, and replication termination and cell division. The bacterium Vibrio cholerae is among the 10% of bacteria known to have their genome divided among more than one chromosome. The two chromosomes differ in terms of replication and segregation machineries, as the second chromosome, like all bacterial secondary chromosomes, is derived from a plasmid acquired by the common ancestor of the vibrios. The structure of the chromosomes in this organism is currently unknown. This thesis details the construction of a recombination-based system designed to explore the two-chromosome genomic structure of V. Cholerae. This tool builds on a recombination system used to describe the chromosome structure of Escherichia coli, and expands its use for bacteria with multiple chromosomes, working in a manner similar to recombination cassette mediated exchange (RCME) systems. Using this tool, we demonstrate that the terminus regions of the V. Cholerae chromosomes come into physical contact with one another. This work sets the stage for a full-scale study of the V. Cholerae genome
La majorité des bactéries ont leur génome organisé en un seul chromosome circulaire. Ces chromosomes sont organisés en régions spatialement confinés, qui sont caractérisés par des fréquences de contact faible entre les loci dans les régions différentes. Ces régions sont formées à la suite de processus liés à la transcription des gènes, la réplication et à la ségrégation des chromosomes, et la terminaison de la réplication et la division cellulaire. La bactérie Vibrio cholerae est parmi les 10 % des bactéries connues pour avoir leur génome divisé entre plusieurs chromosomes. Les deux chromosomes diffèrent en termes de mécanismes de réplication et de ségrégation, car le deuxième chromosome, comme tous les chromosomes bactériens secondaires, est dérivé d'un plasmide acquis par l'ancêtre commun des vibrions. La structure des chromosomes dans cet organisme est actuellement inconnue. Cette thèse détaille la construction d'un système basé sur la recombinaison conçu pour explorer la structure génomique de deux chromosomes de V. Cholerae. Cet outil prend appui sur un système de recombinaison utilisé pour décrire la structure du chromosome d'Escherichia coli, et son utilisation peut être élargie aux bactéries avec de multiples chromosomes, en travaillant d'une manière similaire aux systèmes de « Recombinase-mediated cassette exchange » (RMCE). En utilisant cet outil, nous démontrons que les régions terminales des chromosomes de V. Cholerae entrent en contact physique avec l'autre. Ce travail ouvre la voie à une étude à grande échelle du génome de V. Cholerae

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25

Pulicani, Sylvain. "Lien entre les réarrangements chromosomiques et la structure de la chromatine chez la Drosophile". Thesis, Montpellier, 2018. http://www.theses.fr/2018MONTS105/document.

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Entre espèces, les génomes présentent des différences dans leur organisation, que ce soit au niveau du caryotype ou de l'ordre des gènes. Ceci reste vrai même entre espèces relativement proches comme l'humain et la souris, et est du aux réarrangements chromosomiques. Reconstruire l'histoire évolutive d'une lignée revient donc à déterminer des scénarios de réarrangements qui transforment un génome actuel en un autre. Le génome ancestral se trouve alors être l'un des états intermédiaires atteint par l'un de ces scénarios.Les réarrangements chromosomiques sont des évènements biologiques violents pour la cellule. En effet, de nombreux mécanismes moléculaires ont pour fonction de stopper le cycle cellulaire dans le cas où le génome aurait été altéré. De plus, les réarrangements peuvent être à l'origine de phénotypes aberrants, et donc probablement désavantageux pour leur porteur. Au vu de tout cela, il paraît raisonnable de poser l'hypothèse selon laquelle les scénarios de réarrangements sont parcimonieux.Cependant, il est admis que ce seul critère ne permet pas de reconstruire efficacement l'histoire évolutive des génomes. En effet, quelque soit le modèle utilisé pour générer les scénarios, leur nombre est exponentiel en le nombre de réarrangements. Une autre contrainte biologique doit donc être ajoutée. La conservation de la structure spatiale de la chromatine pourrait être un critère manquant essentiel. Il a été montré in vitro que lors d'une cassure double-brin suivie d'une réparation non-homologue, le brin utilisé pour la réparation se situe spatialement proche de la cassure. Notre hypothèse est donc que les points de cassures qui sont proches en 3D ont plus probablement participé à des réarrangements que les autres. Cela est appuyé par des analyses génomiques sur des cellules somatiques et entre espèces. Nommons cette hypothèse: l'hypothèse de localité.Notre approche a été de proposer une méthode pour utiliser l'information structurale afin de prioriser les scénarios de réarrangements. Les données de Hi-C ont été l'information structurale qui nous a permis d'appliquer la méthode aux scénarios entre D. melanogaster et D. yakuba.Ces résultats nous ont ensuite menés à nous demander si la structure de la chromatine ne pouvait pas elle-même évoluer. Elle serait alors susceptible d'être considérée comme un caractère phylogénétique. Cette idée est appuyée par d'autres résultats montrant la conservation de domaines topologiques entre espèces.Cette question ne semble pas avoir été posée auparavant. Elle est pourtant très intéressante car elle permet d'ouvrir tout un champ d'étude. En effet, si la structure de la chromatine porte un signal phylogénétique, alors il devient possible de s'interroger sur les mécanismes en œuvre lors de la sélection, ou sur la possibilité de reconstruire l'état ancestral de cette structure. Par la suite, il serait même possible de comparer l'évolution de la séquence et celle de la structure de la chromatine.Nous avons ainsi défini une distance entre les structures des génomes, basée sur la comparaison des contacts entre loci orthologues. Nous l'avons appliquée à une ensemble de six espèces comprenant l'humain, la souris et quatre drosophiles. Ces résultats confirment la présence d'un signal phylogénétique dans la structure spatiale des génomes. Ils mettent également en lumière l'intérêt de la mise en place de méthodes permettant de comparer efficacement des données de contacts entre espèces
Different species have different genome organization. Whether it be the karyotype or gene order, these differences are seen even with relatively close species like Human and Mouse. This is caused by the chromosomal rearrangement. Infererence of rearrangement scenarios that transform one present-day species into another can give insight into evolutionary states, the ancestral genome being one of the intermediates of the true scenario.The chromosomal rearrangements are violent biological events for the cell. Indeed, numerous mechanisms are present to stop the cell cycle when the genome sequence is altered. Moreover, rearrangements can be the source of aberrant phenotypes, which are probably unfavorable for the carrier. With all that, it seams reasonable to assume the rearrangement scenarios are parsimonious.However, it is accepted that this criterion alone is not sufficient to efficiently build the evolutionary history of the genomes. Indeed, for whatever model we choose, the number of scenario is exponential in the number of rearrangements. Another biological constraint is needed. The spatial structure of the chromatin could be an essential missing criterion. It has been shown in vitro that when a double-stranded break of the DNA is non-homologously repaired, the strand used for repairing is close in space to the breakpoint. Our hypothesis is that the closer the breakpoints are in space, the more probable they are to participate in a rearrangement. This hold on genomics analysis of somatic cells, and between species. Let's name that hypothesis the locality hypothesis.We proposed a method to use the structural information in order to prioritize the rearrangements scenarios. The Hi-C data were the structural information that allowed us to apply our method to scenarios between D. melanogaster and D. yakuba.This results led us to ask whether the chromatin structure could evolve by itself. Then, it could be used as a phylogenetic mark. This idea is related to previous results showing the conservation of topological domains between species.This question seams to be new, and could open a new line of investigation. If the chromatin structure holds a phylogenetical signal, it becomes possible to ask ourselves about the mechanisms that occur during the selection, or if it is possible for the ancestral state to be inferred. Then, it could even be possible to compare the evolution of the sequence with the one of the chromatin structure.Thus, we defined a distance between genome structures, based on the comparison of contacts between orthologous loci. We applied this distance to a set of six species, including the Human, the Mouse and four Drosophila. This result confirms the presence of a phylogenetic signal in the spatial structure of the genomes. They also showed that we're in need for efficient methods to compare contacts data between species

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West, Allan. "Investigating the links between meiotic chromosome structure and homologous recombination in Arabidopsis thaliana". Thesis, University of Birmingham, 2015. http://etheses.bham.ac.uk//id/eprint/6399/.

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Accurate chromosome segregation during meiosis requires the reciprocal exchange of DNA between homologous chromosomes, via a process called homologous recombination, resulting in the formation of crossovers (COs). This process begins with the formation of programmed DNA double-strand breaks (DSBs). Certain genomic loci, called hotspots, are more likely than others to produce DSBs. This is thought to be determined by various factors, which include post-translational histone modifications, such as H3K4 trimethylation. The histone methyl-transferase AtSDG2 is largely responsible for the deposition of this histone mark. This research shows that CO frequency and distribution are altered in an $Atsdg2$ background. Study of a mutant allele of a gene which codes for a subunit of a histone-acetyl transferase complex, called AtMRG2, revealed a strongly reduced fertility phenotype and failure to produce DSBs. Further study revealed that the defects were due to mutation to the $AtPRD3$ gene, known to be essential for DSB formation, and that the mutation to $AtMRG2$ was not responsible. During meiosis, homologous recombination takes place in the context of specific structural arrangement of DNA organised as an array of loops emanating out from a proteinaceous axis, a major component of which is AtASY1. My studies demonstrate that the dynamics of AtASY1 are affected by mutation to AtPCH2, an AAA+ ATPase, and that formation of the synaptonemal complex is perturbed. $Atpch2$mutants initiate DSB formation and CO designation normally, but defects occur in CO maturation, causing a reduced CO frequency and formation of univalent chromosomes at metaphase I. Finally, the effects of temperature on the structure of meiotic chromosomes and homologous recombination were studied by cytological analysis of Col 0 and different meiotic mutants subjected to a range of temperatures for the duration of meiosis. I have demonstrated that certain mutations, such as $Atsdg2$ and $Atpch2$, confer some resistance to the effects of high (32˚C) temperature treatment, which causes various meiotic defects in Col 0.

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BARRETO, L. M. "Estudos Citogenéticos em Dorstenia L. (Moraceae)". Universidade Federal do Espírito Santo, 2016. http://repositorio.ufes.br/handle/10/7838.

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Made available in DSpace on 2018-08-01T22:57:27Z (GMT). No. of bitstreams: 1 tese_10051_Dissertação Final Lucas Mesquita Barreto.pdf: 1926946 bytes, checksum: 21145320a1a7d898eb87b86e37b7dd01 (MD5) Previous issue date: 2016-07-18
Previous cytogenetic studies in Dorstenia mention that the species may have 24 to 72 chromosomes, and suggested a conserved chromosome number 2n = 32 for the Neotropic species. However, some information reported in the literature are dubious or insufficient to assess the potential of cytogenetic data to the better understand of systematics and evolution issues within this genus. Here, eight species of Neotropical Dorstenia had their karyotypes characterized, and the nuclear DNA content measured. Dorstenia bahiensis, D. cayapia, D. grazielae, D. hirta and D. turnerifolia had their karyotypes characterized and the DNA nuclear content measured for the first time. Morphological plant characters and morphometric data were submitted to cluster analysis, followed by a test of group sharpness, and ordination analysis, aiming to support the discussion about the potential of cytogenetic data to infrageneric systematic of Dorstenia. The species showed chromosome number of 2n = 32, varying in chromosomes morphology. The karyotypes least asymmetric were observed in Dorstenia elata, and the more asymmetric were registered in D. bahiensis and D. bonijesu. The 2C value ranged from 3.21 picograms (pg) D. bahiensis to 5.47 pg in D. arifolia. Morphologically similar species, like D. hirta and D. turnerifolia, grouped together based on morphometric data. The sharp groups based on morphometric data correspond to species circumscribed under the sections Dorstenia, Lecania and Emygodia, previously established based on the plant morphology. Our results supports that the chromosome number 2n = 32 is possible conserved in the Neotropical species of Dorstenia, and indicate the potential of cytogenetic data to the systematics of this genus.

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Sabir, Kenneth Spencer. "Visual Analytics Of 3D Macro Molecular Structure". Thesis, The University of Sydney, 2018. http://hdl.handle.net/2123/18860.

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Currently, molecular biology research is dominated by the rapid advances in DNA sequencing and related technologies. However, interpreting these data, and gaining insight into underlying molecular processes, remains challenging. Of the many strategies being pursued in this effort to understand the biomolecular machinery of life, one of the most enduring involves considering three-dimensional structure. Increasingly, experimental data is providing information on this 3D structure and dynamics of chromosomes in living cells –– these data, in turn, promise new insight into fundamental genomic processes. Similarly, the flood of DNA and protein sequence data provides a vast resource that can be used to greatly extend our ability to predict the 3D structure of proteins. In this thesis I describe Score, a visual analytics framework I have created to help biologists understand the 3D structure of chromosomes and proteins, and to explore how this structure relates to the underlying biological function. Usage of the Score framework is demonstrated through two case studies: Aquaria and Rondo. Aquaria is a web-based protein sequence structure viewer allowing users to find and navigate through structures for any given protein sequence. Rondo is a web-based chromosome structure viewer that can superimpose feature track information.

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Caravaca, Guasch Juan Manuel. "Elementos estructurales de la cromatina en los cromosomas mitóticos". Doctoral thesis, Universitat Autònoma de Barcelona, 2004. http://hdl.handle.net/10803/3520.

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Nuestro grupo ha estudiado la estructura de la cromatina de núcleos de eritrocitos de pollo (Bartolomé et al., 1994; Bartolomé et al., 1995; Bermúdez et al., 1998). La consecuencia de estos estudios ha sido la elaboración de un modelo para el plegamiento de la fibra de cromatina con una elevada concentración local del DNA (Daban y Bermúdez, 1998; Daban, 2000). Sin embargo, el nivel máximo de condensación en la cromatina, se encuentra en el interior de los cromosomas metafásicos. Aunque la bibliografía ha planteado diferentes modelos para el plegamiento de la cromatina en el interior de éstos, existe un conocimiento muy escaso acerca de la estructura molecular de la cromatina en los cromosomas condensados.
Se ha realizado un estudio exhaustivo de microscopía electrónica de transmisión sobre la estructura de los cromosomas metafásicos de células HeLa. Se han estudiado un total de 4410 micrografías de cromosomas metafásicos, que en su mayor parte han sido tratados con diversos medios parcialmente desnaturalizantes, para poder analizar su estructura interna.
Morfológicamente, los cromosomas estudiados en este trabajo pueden agruparse en tres tipos diferentes: compactos, granulados y fibrilados. La morfología más abundante es la compacta y se observa en presencia de cationes monovalentes y divalentes a concentración similar a la presente en la cromatina metafásica (Mg2+ 1.7-40 mM). Estos cromosomas tienen las cromátidas muy densas y en sus bordes se aprecian una serie de estructuras planas superpuestas. En condiciones de menor concentración de cationes (Mg2+£ 1.7 mM), la morfología dominante es la granular. Estos cromosomas están compuestos principalmente por gran cantidad de cuerpos circulares de 30-40 nm de diámetro. Únicamente en condiciones de fuerza iónica extremadamente baja podemos encontrar la morfología fibrilar, la cual se caracteriza por la abundancia de fibras de 30-40 nm.
Los resultados obtenidos con cromosomas parcialmente desnaturalizados nos permiten concluir que existen tres elementos estructurales en el interior de los cromosomas metafásicos: la fibra, el gránulo y la placa.
Las fibras gruesas con diámetros que oscilan entre los 100 y los 500 nm son el resultado de la deformación plástica de las cromátidas durante los diferentes procesos de preparación de las muestras. En función de las condiciones iónicas del medio las fibras gruesas muestran gránulos o placas en su interior. Las fibras delgadas están formadas por una sucesión de cuerpos de 30-40 nm de diámetro unidos irregularmente mediante interacciones cabeza-cola. Las fibras delgadas se observan dominantemente en condiciones de concentración salina extremadamente baja.
Los gránulos son unos cuerpos circulares compactos de unos 30-40 nm de diámetro. Estos cuerpos compactos descritos previamente por nuestro grupo y se interpretaron como una forma de plegamiento solenoidal de la fibra de 30 nm (Daban y Bermúdez, 1998). Se encuentran presentes en todas las condiciones estudiadas en este trabajo, siendo especialmente abundantes en presencia de iones divalentes a concentración baja y en muestras tratadas con nucleasa micrococal.
La placa es un elemento estructural característico de los cromosomas cuando éstos se encuentran en su forma más compacta, en presencia de concentraciones elevadas de cationes divalentes. Esta estructura no había sido descrita previamente por otros laboratorios. Es una estructura cromatínica de gran regularidad y con una superficie muy lisa. Hemos estimado la altura de estas placas a través de muestras sombreadas unidireccionalemente con platino. El promedio de los valores obtenidos es de 6.7 ± 1.4 nm.
En conjunto los resultados obtenidos en esta tesis permiten sugerir que el componente principal de la cromatina en los cromosomas metafásicos es el gránulo de 30-40 nm. Dependiendo de las condiciones iónicas, este elemento estructural fundamental se agrega a través de uniones cabeza-cola para formar fibras (fuerza iónica muy baja), o bien se agrega mediante interacciones laterales para formar placas (condiciones salinas próximas a las de la cromatina metafásica).
Our group has studied the chromatin structure in the chicken erythrocyte nuclei (Bartolome et al., 1994; Bartolomé et al., 1995; Bermúdez et al., 1998). The consequences of this studies has been the elaboration of a folding model of the chromatin fiber with a high local concentration of DNA. However, the maximum level of chromatin condensation, is found in the metaphase chromosomes. Although the bibliography has proposed different models to explain the chromatin folding inside the chromosomes, there is a low knowledge about the molecular structure of chromatin in the condensed chromosomes.
In this thesis, we have carried out an exhaustive electron microscopy study about the HeLa cells metaphase chromosomes. We have studied a large number of chromosome electron micrographs (4410). Chromosomes were partially denaturated under a wide variety of conditions in order to observe some chromatin structural element inside them.
Our studies indicate that chromosomes can adopt three global structural forms in function of the ionic conditions: compact, granular and fibrillar.
The compact form is the most frequent and we can observe it in the presence of monovalent and divalent cations in similar concentrations than the ones found in metaphase chromatin (Mg2+ 1.7-40 mM). These chromosomes have highly condensed chromatids and we can appreciate overlapped chromatin plates around the chromosomes edges. When the chromosomes are incubated with solutions containing lower cations concentration (Mg 2+£ 1.7 mM) they become granular. The granular structures seen inside these chromosomes show a diameter of about 35 nm. Fibrillar chromosomes are observed only at very low ionic strength. The fibers seen emanating from the chromatids have a diameter of 30-40 nm.
Our results obtained from partially denaturated chromosomes show that there are three structural elements inside the metaphase chromosomes: the fiber, the 30-40 nm chromatin granule and the plate.
The largest fibers with a diameter of 100-400 nm, presumably are produced by mechanical deformation of chromosomes during the preparation processes. Depending of the ionic conditions these fibrillar structures are composed by plates or granules. The thinnest fibers are formed by face to face association of the 30-40 nm chromatin granules. These kind of fibers are usually found only at very low ionic strength.
The chromatin granules are compact bodies with 35 nm of diameter. These compact bodies were previously described in our laboratory and were modeled as compact solenoids of nucleosomes forming (Daban and Bermúdez, 1998). They are usually seen at low divalent cation concentrations and in chromosome samples treated with micrococal nuclease.
The plate is the most frequent structural element when the chromosomes are in their compact form (high ionic strength, similar to physiological conditions). This element has not been described by any group. It is a chromatin element with a regular structure and very smooth surface. We have estimated the height of the steps between layers in unidirectional shadowing experiments. The value obtained is 6.7 ± 1.4 nm.
Our results suggest that the fundamental component inside the metaphase is the 30-40 nm chromatin granules. Depending of the ionic conditions, this basic structural element forms fibers through face to face interactions (very low ionic strength) or form plates through side to side interactions (high ionic strength similar to metaphase chromatin).

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Oakey, Rebecca. "The structure of alphoid satellite DNA on normal and abnormal human Y chromosomes". Thesis, University of Oxford, 1989. http://ora.ox.ac.uk/objects/uuid:162cb1a7-3176-4b56-be8b-353b65fee236.

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The long-range structure of the Y chromosome alphoid satellite DNA has been determined in the cell lines 3E7 and OXEN. Variation in alphoid DNA block size and restriction enzyme sites were observed. The alphoid block size and restriction enzyme site variations were determined for a collection of 42 normal Y chromosomes. The alphoid DNA polymorphisms observed denned 24 Y chromosome alleles. Unexpectedly, the Y alphoid DNA alleles analysed revealed two distinct groups of Y chromosomes indicating that most of the Caucasian and Asian men analysed were descended from one of two males. The structure of the alphoid DNA was determined for 25 cell lines expected to contain abnormal Y chromosomes. Six of the cell lines lacked Y chromosomes. Four lacked both alphoid DNA and Y a centromere. 13 out of the remaining 15 Y chromosomes had centromeres and Y alphoid DNA block sizes and restriction enzyme site variation similar to that of normal Y chromosome alphoid DNA. Two of the abnormal cell lines had alphoid DNA blocks significantly different from the normal Y alphoid DNA structure. These results confirm that alphoid DNA is located very close to, or at the centromere and make it a prime candidate for a functional mammalian centromere sequence.

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VENEZIANO, BROCCIA PAMELA. "Role of RNA:DNA hybrids management in controlling mitotic chromosome structure in human cancer cells". Doctoral thesis, Università degli Studi di Trieste, 2021. http://hdl.handle.net/11368/2988915.

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R-loops are three-stranded nucleic acid structures that contain RNA paired with its antisense DNA template and a loop of displaced single-stranded DNA (ssDNA). RNA-DNA hybrids formation occurs in a natural context and has been demonstrated to critically impact on epigenetic gene regulation. However, persistent RNA:DNA hybrids have been shown to cause replication stress, chromosome fragility, mitotic defects, and chromosome rearrangements. We found that the RNA-binding protein SFPQ has a critical role in maintaining genome stability by resolving RNA:DNA hybrids at telomeres of vertebrate cells. Starting from this work, we found that SFPQ function is not limited to telomeres but has a critical role in stabilizing repeat rich regions across genome including pericentric regions. Loss of SFPQ alters cell cycle progression and triggers mitotic defects such as chromatin bridges and multilobed cells. We found that SFPQ has a role in preventing sister chromatid exchange, aberrant chromosome architecture and altered sister chromatid cohesion. Our data suggest an involvement of SFPQ and RNA:DNA hybrids in controlling mitotic chromosome structures and faithful chromosome segregation in mitosis. Together, our results indicate a role for SFPQ as important regulator of RNA:DNA hybrid related genomic instability.

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Fitz-James, Maximilian Hamilton. "Investigation of the chromatin composition and structure of foreign DNA in a mammalian cell". Thesis, University of Edinburgh, 2018. http://hdl.handle.net/1842/33126.

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In order to contain many millions, or even billions of base pairs within every nucleus of a eukaryotic cell, DNA must be extensively packaged. This is achieved by association of DNA with packaging proteins, resulting in the formation of chromatin, which can lead to various degrees of compaction. The most extreme form of compaction is the highly condensed mitotic chromosome, formation of which is necessary for proper resolution and segregation of the genetic material during cell division. However, the exact nature of the structure of chromatin within the mitotic chromosome and the factors which regulate it remain subjects of debate and continued investigation. The hybrid cell line F1.1 presents a unique tool for the study of mitotic chromosome structure. This mouse cell line has been observed to present a distinct chromatin structure in mitosis assembled over a large region of DNA inserted into one of its chromosomes and originating from the fission yeast Schizosaccharomyces pombe. Direct comparison of the structure of this distinct region of chromatin with that of the adjacent endogenous chromatin could provide insight into the nature of mitotic chromosome structure as well as the properties of the chromatin which are influencing this structure. Microscopy and Hi-C analyses showed that the mitotic chromatin organising or "scaffold" proteins are not altered over the region of S. pombe chromatin, but that the amount of chromatin organised around these proteins is diminished. In accordance with the "radial-loop" model of mitotic chromosome structure, we put forward a model whereby the S. pombe chromatin is organised into smaller chromatin loops around a constant organising scaffold. Examination of the histone post-translational modifications over the region of S. pombe chromatin revealed it to be highly heterochromatic, with high levels of H3K9me3 and associated factors such as HP1α and 5meC, and low levels of activating marks. Generation of further mammalian - S. pombe fusion cell lines recapitulated both the distinct mitotic structure and the heterochromatic profile of the inserted S. pombe chromatin. However, insertion of S. pombe DNA into a mouse cell by transfection rather than fusion resulted in a large region of S. pombe DNA that lacked both a distinct structure and heterochromatin. These results suggest that H3K9me3- mediated heterochromatin may influence the structure of chromatin in mitosis, leading to an organisation into smaller chromatin loops than non-heterochromatic regions.

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Garmendia, Eva. "A Unified Multitude : Experimental Studies of Bacterial Chromosome Organization". Doctoral thesis, Uppsala universitet, Institutionen för medicinsk biokemi och mikrobiologi, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-332471.

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Bacteria are many, old and varied; different bacterial species have been evolving for millions of years and show many disparate life-styles and types of metabolism. Nevertheless, some of the characteristics regarding how bacteria organize their chromosomes are relatively conserved, suggesting that they might be both ancient and important, and that selective pressures inhibit their modification. This thesis aims to study some of these characteristics experimentally, assessing how changes affect bacterial growth, and how, after changing conserved features, bacteria might evolve. First, we experimentally tested what are the constraints on the horizontal transfer of a gene highly important for bacterial growth. Second, we investigated the significance of the location and orientation of a highly expressed and essential operon; and we experimentally evolved strains with suboptimal locations and orientations to assess how bacteria could adapt to these changes. Thirdly, we sought to understand the accessibility of different regions of the bacterial chromosome to engage in homologous recombination. And lastly, we constructed bacterial strains with chromosomal inversions to assess what effect the inversions had on growth rate, and how bacteria carrying costly inversions could evolve to reduce these costs. The results provide evidence for different selective forces acting to conserve these chromosome organizational traits. Accordingly, we found that evolutionary distance, functional conservation, suboptimal expression and impaired network connectivity of a gene can affect the successful transfer of genes between bacterial species. We determined that relative location of an essential and highly expressed operon is critical for supporting fast growth rate, and that its location seems to be more important than its orientation. We also found that both the location, and relative orientation of separated duplicate sequences can affect recombination rates between these sequences in different regions of the chromosome. Finally, the data suggest that the importance of having the two arms of a circular bacterial chromosome approximately equal in size is a strong selective force acting against certain type of chromosomal inversions.

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Fung, King-leung. "Molecular study of the deleted in liver cancer 2 (DLC2)h[electronic resource] : solution structure of the SAM domain and interaction with MCM7 /". Click to view the E-thesis via HKUTO, 2005. http://sunzi.lib.hku.hk/hkuto/record/B36218716.

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Pingault, Lise. "Analyses structurales et fonctionnelles de l'espace génique du chromosome 3B du blé tendre (Triticum aestivum L.)". Thesis, Clermont-Ferrand 2, 2014. http://www.theses.fr/2014CLF22504/document.

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De par sa taille (17 Gb), la complexité de son génome (allohexaploïde) ainsi que la forte proportion d’éléments répétés (>80%), l’étude du génome de blé tendre est une tâche particulièrement complexe et s’est souvent retrouvée confrontée aux limites technologies. Grâce une approche de tri de chromosomes, le chromosome 3B (995 Mb) a pu être isolé et séquencé. Ces données ont permis la construction d’une pseudomolécule. Mes travaux de thèse se sont basés sur des données de transcriptomique produites avec une approche RNA-Seq, afin d’investiguer l’impact de la taille de ce chromosome sur l’organisation de l’espace génique. L’annotation du chromosome 3B a permis de mettre en évidence : 5 326 gènes et 1 938 pseudogènes. L’analyse des librairies RNA-Seq pour 15 conditions de développement a permis de mettre en évidence l’expression de 71 % des gènes annotés, ainsi que 3 692 régions nouvellement transcrites (NTR). Nous avons aussi pu détecter des transcrits alternatifs pour 61% des gènes exprimés (en moyenne 6 isoformes). Nous avons donc pu mettre en évidence une structuration de l’espace génique pour le chromosome 3B. En effet, la transcription est répartie sur tout le chromosome, cependant les gènes sont organisés selon un gradient de densité croissant sur l’axe centromère-télomère. En nous basant sur le profil des données de recombinaison, nous avons divisé le chromosome en 3 régions : R1, R2 et R3. La région R2 correspondant à la région centrale du chromosome (647 Mb) où le taux de recombinaison est très faible voir absent. Les régions R1 (58 Mb) et R3 (69 Mb) correspondent respectivement aux parties distales du bras court et du bras long du chromosome, où le taux de recombinaison est le plus fort. Ces trois régions diffèrent par leur niveau et leur spécificité d'expression, ainsi que par leur structure génique (nombre d'exons, taille des introns …). En effet, les gènes ayant une expression tissu-spécifique, ainsi qu’un faible nombre de transcrits alternatifs sont retrouvés dans les régions R1 et R3. Deux modèles peuvent expliquer le lien observé entre la structure des gènes et leur niveau/spécificité d’expression : le modèle de la sélection pour l’économie et le modèle dessin génomique. En conclusion, ce travail a montré et ce, pour la première fois à l’échelle d’un chromosome entier de blé, l’impact de la taille du chromosome sur l’organisation ; mettant en relation la structure des gènes, leur niveau d’expression, leur spécificité d’expression, ainsi que leur nature évolutive. L’assemblage ainsi que l’annotation de pseudomolécules des autres chromosomes permettra de mettre en évidence si cette structure est conservée. Afin de mieux comprendre les mécanismes cellulaires impliqués dans la régulation de l’expression des gènes, une étude du paysage épigénomique a été engagée
Genome-wide studies of the bread wheat are a complicated task due to its large size (17 Gb), its allohexaploidy and its high content in repeat sequences (>80%). Using a chromosome-specific approach, the chromosome 3B (995 Mb) was successfully isolated and sequenced leading to the assembly of one pseudomolecule. The work presented in this thesis investigated the impact of the 3B chromosome size on the gene space organization. Production of transcriptomic data was achieved using RNA-Seq approach. The chromosome 3B was annotated and we predicted 7 264 features, including 5 326 full genes and 1 938 pseudogenes. We constructed RNA-Seq libraries for 15 developmental wheat conditions. Using this data we detected expression of 71.4% of the predictions, and 3 692 novel transcribed regions (NTR). We also detected alternative transcripts for 61% of the expressed genes, with 5.8 isoforms on average for one gene. Using these transcriptional data, we highlighted a partitioning of the chromosome 3B gene space. Indeed, transcription was found all along the chromosome, but genes were organized according to an increasing density gradient along the centromere-telomere axis. Based on recombination profile, we segmented the chromosome in 3 major regions: R1, R2 and R3. The region R2 was identified with low or no recombination rate corresponding to the centromeric and peri-centromeric regions (647 Mb). The regions R1 and R3 were associated with a higher recombination rate, both localized on the distal part of the short arm (58 Mb) and the long arm (69 Mb) respectively, where the recombination rate is higher. All three regions showed distinct level and specificity of gene expression as well as unique gene structure (variation size, exon number, intron size). Indeed, genes expressed in a specific condition and with a small number of alternatives transcripts were localized on regions R1 and R3. We showed that two evolutionary model could explain the link between gene structure and the level/specificity of expression : “selection for economy” and “genome design”. In conclusion, a transcriptomic studies was achieved along the 3B chromosome for the first time. This study demonstrated a relationship between gene characteristics (structure, expression level, expression specificity and evolution) and the chromosome 3B organization. Future pseudomolecule assemblies will help us to assess the structural organization of these chromosomes. In order to better understand the cellular mechanisms of gene expression, an epigenomic study of the 3B chromosome was started

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Redgrave, Liam Stephen. "The role of supercoiling in altering chromosome structure, gene expression and antibiotic resistance in bacteria". Thesis, University of Birmingham, 2017. http://etheses.bham.ac.uk//id/eprint/7912/.

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Antibiotic resistance is a major problem estimated to cost $100 trillion and cause 10 million deaths per year by 2050. Despite novel molecules targeting Gram-positive bacteria, there are no new antibiotics active against Gram-negatives. To prolong use of current drugs, we need to understand mechanisms of resistance to inform prescribing practices and drug discovery. Quinolone resistance is primarily conferred by mutations in the target loci: DNA gyrase (gyrA) and topoisomerase IV. Quinolone resistance arising from gyrA mutations has also been shown to confer a low level of protection against a range of non-quinolone drugs. This thesis investigated the hypotheses that altered supercoiling levels, resulting from gyrA mutations, alter expression of stress response genes and confer a generic protective effect against other antibiotics and chemicals. The effects of equivalent gyrA mutations in Salmonella and E. coli upon supercoiling were analysed. Both GyrA Ser83Phe and GyrA Asp87Gly substitutions resulted in altered topoisomer profiles, although these were different between the species. When exposed to stresses, Salmonella gyrA mutants maintain supercoiling in a relatively fixed manner, providing a degree of antimicrobial protection but possibly limiting flexibility in response to environmental change. Fluorescent reporter assays showed a modest elevation of stress responses in Salmonella GyrA Asp87Gly cells, but highly upregulated stress responses in E. coli GyrA Asp87Gly cells. This correlated with a competitive fitness benefit of E. coli GyrA Asp87Gly cells vs the parent in the presence of low levels of triclosan. The elevated stress responses likely result from supercoiling-induced changes in promoter accessibility, and are probably responsible for the generic protective effect gyrA mutation confers against other chemicals and antibiotics. Non-quinolone antimicrobials can provide a selective pressure that favours gyrA mutants, although this is highly dependent on condition and species.

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Rosa, Alexandra. "Phylogenetic structure of Guinea-Bissau ethnic groups for mitochondrial DNA and Y chromosome genetic systems". Doctoral thesis, Universidade da Madeira, 2007. http://hdl.handle.net/10400.13/38.

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The maternal and paternal genetic profile of Guineans is markedly sub-Saharan West African, with the majority of lineages belonging to L0-L3 mtDNA sub-clusters and E3a-M2 and E1-M33 Y chromosome haplogroups. Despite the sociocultural differences among Guinea-Bissau ethnic groups,marked by the supposedly strict admixture barriers, their genetic pool remains largely common. Their extant variation coalesces at distinct timeframes, from the initial occupation of the area to later inputs of people. Signs of recent expansion in mtDNA haplogroups L2a-L2c and NRY E3a-M2 suggest population growth in the equatorial western fringe, possibly supported by an early local agricultural centre, and to which the Mandenka and the Balanta people may relate. Non-West African signatures are traceable in less frequent extant haplogroups, fitting well with the linguistic and historical evidence regarding particular ethnic groups: the Papel and Felupe-Djola people retain traces of their putative East African relatives; U6 and M1b among Guinea-Bissau Bak-speakers indicate partial diffusion to Sahel of North African lineages; U5b1b lineages in Fulbe and Papel represent a link to North African Berbers, emphasizing the great importance of post-glacial expansions; exact matches of R1b-P25 and E3b1-M78 with Europeans likely trace back to the times of the slave trade.
Orientadores: António Brehm e Richard Villems

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Oudelaar, A. Marieke. "The three-dimensional regulatory landscapes of the globin genes". Thesis, University of Oxford, 2018. http://ora.ox.ac.uk/objects/uuid:6cd793fe-b28a-4d98-a588-b6eec5dfa416.

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One of the most important outstanding questions in biology involves the precise spatial and temporal regulation of gene activity, which enables different cell types to express the specific set of genes required for their function and is therefore a cornerstone for complex biological life. Cis-regulatory elements, such as gene promoters and enhancers, play a key role in controlling gene activity. These elements physically interact with the genes they regulate within structural chromatin domains. The organisation of chromosomes into these domains is critical for specific regulation of gene expression and disruption of these structures underlies common human disease. However, it is not understood how chromatin domains form, how interactions between the cis-regulatory elements contained within them are established, or how such interactions influence gene expression. The major hurdles in addressing these questions are to determine chromatin structures with high resolution and sensitivity and to examine their dynamic nature within single cells. To overcome these, I have developed Tri-C, a new chromosome conformation capture assay that can analyse concurrent chromatin interactions at single alleles at high resolution. By combining Tri-C with conventional chromosome conformation capture techniques, I have analysed the three-dimensional regulatory landscapes of the well-characterised murine globin loci at unprecedented depth. Additionally, to examine the roles of cis-regulatory elements in establishing chromatin architecture, I have analysed how engineered deletions in enhancers and CTCF-binding elements in the murine alpha-globin locus disrupt its chromatin landscape. These analyses reveal that the chromatin domains containing the globin genes represent compartmentalised structures, which are delimited by CTCF boundaries. The heterogeneity of interactions in these domains between individual cells is indicative for a dynamic process of loop extrusion underlying their formation. Within chromatin domains, preferential structures are formed in which multiple enhancers and promoters interact simultaneously. These complexes provide a structural basis for understanding how multiple cis-regulatory elements cooperate to establish robust regulation of gene expression. Importantly, these complex, tissue-specific structures, cannot be explained by loop extrusion alone and indicate other, independent mechanisms contributing to chromosome architecture, likely involving interactions mediated by multi-protein complexes. Together, these analyses show that the current view of genome organisation, in which chromosomes are organised by stable loops and domains that self-assemble into hierarchical structures, is not correct. Rather, chromatin architecture reflects a complex interplay between distinct molecular mechanisms contributing to the formation of regulatory landscapes that facilitate precise, robust control of gene expression.

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Tendeng, Christian. "Structure-fonction-évolution des protéines H-NS chez les bactéries à coloration de Gram négatif". Versailles-St Quentin en Yvelines, 2002. http://www.theses.fr/2002VERS0028.

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La protéine H-NS est impliquée dans le contrôle de l'expression de nombreux gènes chez Escherichia coli. Pourtant, son rôle dans la physiologie bactérienne reste encore énigmatique. La sensibilité d'un mutant hns de E. Coli à l'acide aminé sérine nous a permis d'isoler plus d'une dizaine de protéines homologues chez d'autres bactéries comme Vibrio cholerae, l'agent du Choléra. La caractérisation d'une protéine H-NS chez la bactérie psychrophile Psychrobacter spp. A révélé par ailleurs le rôle essentiel du domaine N-terminal dans la stabilité à la température. A ce jour, plus de quarante protéines de type H-NS ont pu être identifiées, exclusivement chez les protéobactéries. Le rôle premier de la protéine H-NS dans la physiologie d'E. Coli semble se dessiner autour des ARNs et du métabolisme à un carbone
The H-NS protein of Escherichia coli controls the expression of various genes involved in adaptation to environmental challenges. But the function of H-NS in bacterial metabolism remains elusive. Taking advantage of serine susceptibility, we have characterized more than ten H-NS related proteins in other bacteria like Vibrio cholerae. Among them, the characterization of the Psychrobacter H-NS protein from a psychrophilic bacteria reveals the crucial role of the N-terminal domain for the thermal stability of H-NS protein. Currently, more than forty H-NS-like proteins have been identified exclusively from proteobacteria. The importance of RNAs and one carbon metabolism in H-NS functions have been suggested

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40

Sabbaghian, Nelly. "Structure-function analysis of three widely dispersed point mutations in the hormone-binding domain of the androgen receptor". Thesis, McGill University, 1994. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=68254.

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Three point mutations have been found in the hormone-binding domain (HBD) of the human androgen receptor (hAR): one in the N-terminal end (Ile663Asn in a family with partial androgen insensitivity syndrome (PAIS)); one in the middle, (Leu820Val in a family with PAIS); and one in the C-terminal end (Pro903Ser, in a family with complete AIS). The positions 663 and 903 were the most terminal mutation sites in the HBD found to date. The three mutant hARs have been previously characterized biochemically in genital skin fibroblasts. In the family with the Leu820Val substitution, the mother and the grandmother were found to be carriers for the same mutation. To prove their pathogenicity, each of the three mutations has been reproduced in an hAR expression vector that was transfected into COS-1 cells. In COS-1 cells, the complexes from Pro903Ser and Leu820Val had: increased thermolability; increased dissociation rates; decreased affinity; and abnormal transactivation. There was a hierarchy in the severity of the mutations expressed in kinetic and transactivation assays that correlated with the severity of the clinical phenotype. The pathogenicity of the Pro903Ser and the Leu820Val mutations was thereby confirmed. In COS-1 cells, the AR with Ile663Asn had normal thermolability, normal dissociation rates, and normal transactivation, but a decreased affinity. Although this sequence alteration has only been found in a PAIS patient, its pathogenicity is not considered to be proven. More sensitive assays are needed for this purpose.

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Le, Bourgeois Pascal. "Structure et organisation du chromosome de Lactococcus lactis : [thèse en partie soutenue sur un ensemble de travaux]". Toulouse 3, 1993. http://www.theses.fr/1993TOU30095.

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Lactococcus lactis est une bacterie a gram positif employee dans l'elaboration de tres nombreux produits laitiers fermentes. La structure et l'organisation du chromosome de cette bacterie ont ete etudiees par electrophorese en champs pulses. Une carte physique et genetique du chromosome a ete etablie pour deux souches de laboratoire de l. Lactis. Ce travail a necessite le developpement d'outils genetiques originaux. Le plasmide prl1, un plasmide integratif qui permet d'introduire de nouveaux sites de restriction rares au hasard dans le chromosome, a ete utilise pour construire la carte physique du chromosome. La localisation precise des genes sur cette carte physique a ete realisee a l'aide d'un second plasmide integratif, prc1. La carte genetique comprend une vingtaine de marqueurs chromosomiques, et des sequences recurrentes comme les operons ribosomiques et les sequences d'insertion. Bien que les cartes physiques des deux souches etudiees different sensiblement, l'organisation genetique globale semble conservee sur approximativement 1500 kilobases. Ce travail montre que la cartographie chromosomique par electrophorese en champs pulses constitue un outil indispensable pour l'etude du polymorphisme genomique chez lactococcus lactis, et devrait permettre de mieux evaluer la dynamique des chromosomes bacteriens au cours de l'evolution

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42

Smith, Zoe Elizabeth. "Analysis of the 16p telomere to examine the relationship between DNA replication, chromosome structure and gene expression". Thesis, University of Oxford, 1998. https://ora.ox.ac.uk/objects/uuid:fefcbb7b-9829-4a48-8edd-9608a613922d.

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The overall aim of the laboratory is to understand how the human α globin genes are expressed in a tissue-specific and developmental-stage specific manner from their natural chromosomal environment. This gene cluster has been studied in great detail from this point of view, and it now represents an important general model to address how eukaryotic genes are regulated. Ultimately, this information may be important for the further development of strategies for effective gene transfer, particularly for patients who suffer from inherited anaemias which result from abnormal globin gene expression (thalassemias). The human α globin gene cluster is located close to the telomere, in the terminal band of the short arm of chromosome 16 (16p13.3). Many aspects of Î± gene regulation have been studied in detail, including the identification of the structural genes, their proximal regulatory elements (promoters) and distal regulatory element (HS-40). Erythroidspecific trans-acting factors which bind these elements in vitro and in vivo have been identified. In an attempt to define the regulatory domain containing the α genes, the surrounding chromosomal environment (~400kb) has also been extensively studied. The region is fully sequenced, and the chromatin structure, methylation patterns and scaffold attachment sites have been established. Over 100 natural mutants that perturb α globin expression have been characterised and numerous fragments from this region have been analysed in transgenic mice. One potentially important aspect of α globin gene expression that has not been previously examined is DNA replication. Study of replication throughout this particular region provides an excellent opportunity to integrate this information with what is already known about the regulation of the α cluster. Initially, studies were undertaken to analyse the pattern and timing of DNA replication of the human α globin gene cluster and the surrounding chromosomal region in erythroid and non-erythroid cell-types. Replication timing of this region has also been compared in the individual paternal and maternal alleles of chromosome 16. Once the in vivo pattern of replication was established, the role of chromosomal position upon replication timing was assessed by analysing various constructs of the a cluster in transgenic mice. The role of the distal regulatory element HS-40 in influencing the pattern and timing of replication of the extended region has been examined. Naturally-occurring deletions within this region have facilitated the study of the importance of the telomere and subtelomeric region in determining the replication characteristics of this region. Replication has also been studied in another natural mutant, which contains a deletion which may perturb α gene expression by a novel mechanism.

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43

Mitchell, E. L. D. "Studies on the structure of multiple nucleoli and lampbrush chromosome formation in the oocytes of Xenopus laevis". Thesis, University of Liverpool, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.377143.

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44

Renault, Louis. "Structure tridimensionnelle de RCC1, le régulateur de la condensation chromosomique par cristallographie aux rayons X". Université Joseph Fourier (Grenoble ; 1971-2015), 1998. http://www.theses.fr/1998GRE10104.

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Rcc1, pour regulateur de la condensation chromosomique, est le facteur d'echange du nucleotide guanine de la proteine nucleaire ran (ras-like nuclear g protein) fixant le gtp. Le couple ran-rcc1 est implique dans deux majeurs fonctions cellulaires : la regulation du cycle cellulaire et le transport nucleocytoplasmique. La sequence de la proteine rcc1 est composee de 7 motifs de 51 a 68 acides amines que l'on retrouve egalement chez d'autres proteines non homologues. Nous avons resolu la structure de la proteine a la resolution de 1,7 a par la methode sir (single isomorphous replacement) combinee avec moyennation non-cristallographique (axe non-cristallographique d'ordre 3). Rcc1 est une structure composee de feuillets beta composant une helice de bateau avec 7 pales constituees par les 7 domaines repetes de la sequence. La structure montre une construction differente des structures en helice de bateau de type wd 40 trouvees pour la sous-unite des proteines g heterotrimeriques. Le type de structure de rcc1 en unites repetees fournit une explication pour une serie de mutations pleiotropiques dans s. Cerevisiae, s. Pombe et la lignee cellulaire de hamster tsbn2, qui destabilisent le repliement en helice de bateau, et permet, en s'appuyant sur des donnees de mutagenese dirigee, d'identifier le site d'interaction avec ran sur une des faces de l'helice de bateau ainsi que le site d'interaction de rcc1 avec l'adn sur l'autre face.

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45

Fung, King-leung, e 馮景良. "Molecular study of the deleted in liver cancer 2 (DLC2)h[electronic resource]: solution structure of the SAM domain and interaction withMCM7". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2005. http://hub.hku.hk/bib/B36218716.

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46

Generoso, Serena Francesca 1988. "A Screen for novel factors involved in pluripotency and X-chromosome reactivation". Doctoral thesis, Universitat Pompeu Fabra, 2019. http://hdl.handle.net/10803/666581.

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X-Chromosome Reactivation (XCR) occurs in the epiblast cells of the blastocyst and in germ cells, thereby coupling XCR with pluripotency. We performed a screen in iPS cells by knocking down the expression of candidate genes picked from a single cell microarray expression profile in blastocysts. We thereby identified candidates which had an effect on both pluripotency and X-Reactivation. However, we also identified factors with a specific role in XCR. This suggests that XCR is not an absolute requirement for iPSC reprogramming and that the two processes can be uncoupled. Among these factors, there was the cohesin complex member Smc1a. In experiments based on Super resolution microscopy (STORM), we observed a preferential enrichment of Smc1a on the active compared to inactive X, suggesting a role in shaping the Xa structure. Therefore, we conclude that cohesin-mediated changes in X-chromosome structure are a key step during the XCR process.
La reactivación del cromosoma X (XCR) ocurre en las células epiblásticas del blastocisto y en las células germinales, acoplando XCR con la pluripotencia. Se realizó un cribaje durante la reprogramación de iPSC reduciendo la expresión de genes candidatos, seleccionados a partir de un microarray de expresión en blastocitos. Se identificaron factores con un efecto tanto en la pluripotencia como en la XCR y factores con un rol específico en la XCR. Esto sugiere que la XCR no es un requisito absoluto para la reprogramación de las iPSC, y que los dos procesos se pueden desacoplar. Se identificó el miembro Smc1a del complejo de cohesina. Mediante microscopía de súper resolución (STORM) se observó un enriquecimiento preferencial de Smc1a en el cromosoma X activo en comparación con el X inactivo, lo que sugiere un papel en la configuración de la estructura del X activo. Por lo tanto, concluimos que los cambios mediados por cohesina en la estructura del cromosoma X son un paso clave durante el proceso de XCR.

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47

Varney, Robin Lynne. "Assessment of nuclear DNA variation and population structure in the eastern oyster, Crassostrea virginica, through discovery and analysis of single nucleotide polymorphisms (SNPs)". Access to citation, abstract and download form provided by ProQuest Information and Learning Company; downloadable PDF file, 216 p, 2009. http://proquest.umi.com/pqdweb?did=1891582831&sid=1&Fmt=2&clientId=8331&RQT=309&VName=PQD.

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48

Graham, James Edward. "Structure-function studies of the bacterial dsDNA translocase FtsK". Thesis, University of Oxford, 2010. http://ora.ox.ac.uk/objects/uuid:3f4d5ee0-09fa-482b-a90c-62f3acfc788b.

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DNA translocases are molecular motors that use energy from nucleotide triphosphate (NTP) hydrolysis to move along, pump, remodel or clear DNA. Unlike helicases, double-stranded DNA (dsDNA) translocases do not unwind DNA; their action has no net product apart from inducing supercoils as a result of groove-tracking, which has hampered their characterisation. Many dsDNA translocases appear to have biased directionality. However, the inherent symmetry of dsDNA requires that translocase activity is regulated by specific sequences or through modulation by interaction partners. FtsK is a highly conserved bacterial cell-division protein, localised to the dividing septum, that coordinates chromosome segregation with cytokinesis. It is responsible for the resolution of chromosome dimers by activating the tyrosine recombinases XerCD bound to the 28bp chromosomal site dif. The C-terminal domain of FtsK (FtsKC) is a dsDNA translocase (speed ~5 kb/s, stall force ~60 pN) most closely related to superfamily 4 helicases and is active as a hexameric ring. A winged-helix subdomain at the C-terminus of FtsKC, FtsKgamma, binds to specific 8 bp sequences, KOPS, that are polarised in the bacterial chromosome from the origin to towards dif. FtsKgamma also interacts with XerD, activating it for catalysis. Studies of FtsK translocation have differed over whether KOPS act as a loading or a reversal sequence for FtsK. In Chapter 2, I use a continuous ensemble assay for dsDNA translocation to show that FtsK initiates rapidly at KOPS, with loading dependent on FtsKgamma. Translocation requires moderately cooperative ATP binding, while ATP hydrolysis has a more relaxed cooperativity. I have determined the ATP coupling efficiency of translocation to be ~1.6 bp/ATP, in line with theoretical estimates. Though FtsK probably strips most proteins from DNA, I show in Chapter 3 that FtsK stops translocating when it encounters XerCD bound to dif. The interaction is most likely a specific down-regulation, but surprisingly does not depend on FtsKgamma or on the catalytic or synaptic activity of XerCD. In Chapter 4, I show some preliminary structural data of FtsKC bound to dsDNA, with the aim of determining the first high resolution structure of a ring dsDNA translocase bound to nucleic acid.

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Xiang, Wanqing [Verfasser], e Jan [Akademischer Betreuer] Ellenberg. "Structure and Dynamics of Replication Domains in Single Chromosome Territories of Interphase Nuclei / Wanqing Xiang ; Betreuer: Jan Ellenberg". Heidelberg : Universitätsbibliothek Heidelberg, 2017. http://d-nb.info/1178010597/34.

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50

Oldfield, Andrew. "Etude du réseau transcriptionnel du gène Xist, acteur principal de l'inactivation du chromosome X". Phd thesis, Université Pierre et Marie Curie - Paris VI, 2010. http://tel.archives-ouvertes.fr/tel-00815096.

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L'inactivation du chromosome X est la réponse trouvée par l'évolution pour pallier à la divergence gonosomique entre mâle (XY) et femelle (XX). Ce phénomène sert donc à mettre les deux sexes sur un pied d'égalité en limitant la quantité de transcrits provenant des chromosomes X présents dans les cellules femelles. Au cours de mon doctorat, j'ai tenté de contribuer à l'étude des mécanismes de régulation transcriptionnelle, notamment l'activation, des deux acteurs principaux de l'inactivation: Xist et Tsix, son transcrit antisens. Pendant ces 4 anne��es, j'ai entrepris de cartographier le profil de fixation de plusieurs protéines le long du locus Xist/Tsix, dans le but de comprendre les mécanismes permettant une surexpression de Xist lors de la disparition de ses facteurs répressifs en cours de différenciation. J'ai donc pu établir un modèle de régulation transcriptionnelle de l'ARN non-codant Xist, impliquant plusieurs protéines connues pour leur rôle dans la régulation transcriptionnelle (CTCF et YY1) aussi bien que dans la formation de structures tridimensionnelles (la cohésine). La pertinence de ce modèle est renforcée par nos études montrant que de nombreux aspects de ce modèle sont conservés à travers l'évolution (notamment chez l'homme). J'ai également pu contribuer à la découverte de nouveaux activateurs de Tsix, certains facteurs de pluripotence se fixant au minisatellite DxPas34 afin de réguler l'élongation de la transcription de l'antisens. Ces résultats apportent donc d'importantes informations concernant les mécanismes régulant la mise en place du phénomène d'inactivation du chromosome X au cours du développement précoce de l'embryon.

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