Dissertations / Theses on the topic 'Genome structure'
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Weintraub, Abraham S. (Abraham Selby). "Transcriptional regulation and genome structure." Thesis, Massachusetts Institute of Technology, 2018. http://hdl.handle.net/1721.1/117886.
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Thesis: Ph. D., Massachusetts Institute of Technology, Department of Biology, 2018.Cataloged from PDF version of thesis. Page 162 blink.
Includes bibliographical references.
The regulation of gene expression is fundamental to the control of cell identity, development and disease. The control of gene transcription is a major point in the regulation of gene expression. Transcription is regulated by the binding of transcription factors to DNA regulatory elements known as enhancers and promoters. This leads to the formation of a DNA loop connecting the enhancer and the promoter resulting in the subsequent transcription of the gene. Thus the structuring of the genome into DNA loops is important in the control of gene expression. This thesis will focus on the role of genome structure in transcriptional regulation. Two key questions in this area that I have attempted to address during my PhD are "how are enhancer-promoter interactions constrained so that enhancers do not operate nonspecifically?" and "are there proteins that facilitate enhancer-promoter looping?" I will describe the identification of DNA loop structures formed by CTCF and cohesin that constrain enhancer-promoter interactions. These structures-termed insulated neighborhoods-are perturbed in cancer and this perturbation results in the inappropriate activation of oncogenes. Additionally, I will describe the identification and characterization of the transcription factor YY1 as a factor that can structure enhancer-promoter loops. Through a combination of genetics, genomics, and biochemistry, my studies have helped to identify insulated neighborhood structures, shown the importance of these structures in the control of gene expression, revealed that these structures are mutated in cancer, and identified YY1 as a structural regulator of enhancer-promoter loops. I believe these studies have produced a deeper understanding of the regulatory mechanisms that connect the control of genome structure to the control of gene transcription.
by Abraham S. Weintraub.
Ph. D.
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Trussart, Marie 1985. "Structure determination of mycoplasma pneumoniae genome." Doctoral thesis, Universitat Pompeu Fabra, 2015. http://hdl.handle.net/10803/552940.
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Des de l’aparició de les tecnologies de seqüenciació d’alt rendiment, els conjunts de dades biològiques han esdevingut cada cop més grans i complexes, la qual cosa els fa pràcticament impossibles d’interpretar manualment. El paradigma de l’aprenentatge automàtic permet fer una anàlisi sistemàtica de les relacions i patrons existents en els conjuts de dades, tot aprofitant l’enorme volum de dades disponibles.
No obstant això, una aplicació poc curosa dels principis bàsics de l’aprenentatge automàtic pot conduir a estimacions massa optimistes, un problema prevalent conegut com a sobreajust. En el camp del plegament de proteïnes, en vam trobar exemples en models publicats que afirmaven tenir un alt poder predictiu, però que es comportaven de forma mediocre devant de dades noves.
En el camp de l’epigenètica, problemes com la falta de reproducibilitat, qualitat heterogènia i conflictes entre replicats esdevenen evidents quan es comparen diferents conjunts de dades de ChIP-seq. Per superar aquestes limitacions vam desenvolupar Zerone, un discretitzador de ChIP-seq basat en aprenentatge automàtic que és capaç de combinar informació de diferents replicats experimentals i d’identificar automàticament dades de baixa qualitat o irreproduïbles.Since the appearance of high throughput sequencing technologies, biological data sets have become increasingly large and complex, which renders them practically impossible to interpret directly by a human. The machine learning paradigm allows a systematic analysis of relationships and patterns within data sets, making possible to extract information by leveraging the sheer amount of data available. However, violations of basic machine learning principles may lead to overly optimistic estimates, a prevalent problem known as overfitting. In the field of protein folding, we found examples of this in published models that claimed high predictive power, but that performed poorly on new data. A different problem arises in epigenetics. Issues such as lack of reproducibility, heterogeneous quality and conflicts between replicates become evident when comparing ChIP-seq data sets. To overcome this limitations we developed Zerone, a machine learning-based ChIP-seq discretizer capable of merging information from several experimental replicates and automatically identifying low quality or irreproducible data.
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Axelsson, Tomas. "Evolution of polyploid Brassica genomes : genome structure and the evolution of duplicated genes /." Uppsala : Swedish Univ. of Agricultural Sciences (Sveriges lantbruksuniv.), 2000. http://epsilon.slu.se/avh/2000/91-576-5768-8.pdf.
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Windsor, Aaron J. "Transposons in Arabidopsis : structure, activity, genome restructuring." Thesis, McGill University, 2001. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=38542.
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In the following study, I have investigated aberrant integration events of the maize Activator/Dissociation ( Ac/Ds) family of transposable elements (TEs) in Arabidopsis. The purpose of the study was twofold: (i) to identify sequence modifications associated with aberrant transposition that are informative regarding the mechanism of Ac/Ds transposition; and (ii) to extend our understanding of the mechanisms by which class II TEs can influence genome structure. This work focuses on a large inversion identified on chromosome II. A lone Ds element comprises one breakpoint of the inversion and the second breakpoint is composed solely of Arabidopsis sequences. The analysis of the sequence modifications present at both breakpoints indicates that the event was precipitated by the abortive transposition of Ds. This is the first event of its kind identified for an Ac/Ds and the event defines a novel mechanism by which these TEs can induce change within a genome. Further, the presence of deletions at both termini of the implicated Ds suggests that the transposition of Ac/Ds involves fully excised intermediates. To obtain further support for this model, a population of Arabidopsis individuals harboring Ds excision events was screened for reintegrated elements. Several integrations were analyzed at the sequence level and compared to wild-type integration sites. While no genome rearrangements were detected, a number of integrations display small deletions within both the Ds termini and the DNA flanking the elements. These results are consistent with the presence of fully excised Ac/Ds intermediates. Further, the results suggest that dissolution of the transposase active complex at different points in the transposition process will result in the formation of distinct aberrant transposition products. During the characterization of the inversion, a novel Arabidopsis TE family, FARE, was identified. The FARE elements are foldback transposons, a heterogeneous and poorly characteri
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Wu, Huan-Lin. "Studies of protein structure and genome evolution." Thesis, University of Bath, 2006. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.432372.
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Majumdar, Rajrupa Sonali. "The conservation of genome structure in Salmonella typhi." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp01/MQ48365.pdf.
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Weber, Claudia. "Genome structure and determinants of rates of evolution." Thesis, University of Bath, 2011. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.557810.
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How might the process of meiotic crossing-over affect the evolution of sequences and genome structure? Much attention has been focussed on the notion that crossing-over modulates the efficacy of selection. Here, we consider how good the evidence for this is. Correlations between recombination and protein rates of evolution, commonly interpreted in the above framework, might be misleading for failing to remove the effects of covariates or misinterpreted by disregarding direct effects of recombination, such as biased gene conversion. Similarly, higher diversity commonly seen in highly recombining domains may not necessarily imply a connection between recombination and diversity. It could, for instance, reflect a covariance with mutation rate variability owing to replication timing effects. This thesis examines not only these links between recombination and gene evolution but in addition asks other recombination-centred questions. Is gene order evolution in part driven by recombination predisposing certain sites to rearrangement? How can we account for the genomic location of recombination? Does, for example, germline expression, recently suggested to predict low recombination rates in mammals, predict recombination rates in flies? With the exception of the second chapter where we investigate the relationship between double strand break formation, recombination and sequence divergence in Saccharomyces cerevisiae, my work considers Drosophila, making use of the 12 genomes resource. While an effect of crossover on divergence owing to more efficient selection cannot be ruled out, we demonstrate that premeiotic double strand breaks also predict slow evolution. Late replication, we show, is associated with increases in both divergence and variation but this does not undermine the recombination-diversity correlation. While recombination is associated with increased rearrangement rates, we find no evidence that germline expressed genes avoid recombination.
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Yamato, Katsuyuki. "Structure and Gene Expression of Rice Mitochondrial Genome." Kyoto University, 1993. http://hdl.handle.net/2433/78042.
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Kyoto University (京都大学)0048
新制・課程博士
博士(農学)
甲第5431号
農博第762号
新制||農||649(附属図書館)
学位論文||H5||N2565(農学部図書室)
UT51-93-F188
京都大学大学院農学研究科農芸化学専攻
(主査)教授 大山 莞爾, 教授 山田 康之, 教授 常脇 恒一郎
学位規則第4条第1項該当
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MERONI, ALICE. "RNA IN DNA: FROM STRUCTURE TO GENOME INSTABILITY." Doctoral thesis, Università degli Studi di Milano, 2018. http://hdl.handle.net/2434/570097.
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The presence of RNA in the genome of living cells is one of the emerging topics of the last two decades and has been implicated in many biological processes. I focused my attention on ribonucleotides (rNMPs) embedded into DNA during genome duplication, as a threat to its integrity. In fact, rNMPs have been classified as the most frequent non-canonical nucleotides introduced during genome duplication by DNA polymerases. Such high incorporation frequency has been related to a physiological role in mismatch repair, but it can be easily turned into a source of genomic instability if rNMPs are not removed from DNA. This task is performed by RNase H activities that enable error-free repair of embedded single and multiple ribonucleotides.
I first approached the issue of ribonucleotides incorporation into DNA from a physical point of view. Utilizing Atomic Force Microscopy I studied how ribonucleotides intrusions impact on DNA structure. The results obtained provided new insights on the structural changes imposed by ribonucleotides persistence into DNA. The other part of my Ph.D. project concerned the study of rNMPs incorporation in vivo, using the budding yeast S. cerevisiae as a model organism. The second aim was to unravel the function of the Translesion Synthesis polymerase η (Pol η) when the genome contains residual ribonucleotides and when deoxyribonucleotides (dNTPs) pools are depleted. We found that DNA polymerase η is responsible for the cell lethality observed when dNTPs are scarce and RNase H activities are defective. Therefore, I explored and characterized this unexpected toxic activity. We propose a model where Pol η supports cell survival in low dNTPs conditions by promoting DNA replication using ribonucleotides. While this activity is normally beneficial to wild type cells, it is highly toxic to cells defective for RNase H activities.
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Neuditschko, Markus. "A whole-genome population structure analysis within cattle breeds." Diss., lmu, 2011. http://nbn-resolving.de/urn:nbn:de:bvb:19-133991.
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Liang, Yajie. "Genome Structure of the Hairy-Root-Inducing Plasmid pRiA4b." 京都大学 (Kyoto University), 2001. http://hdl.handle.net/2433/150895.
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Smith, I. R. L. "Genome structure and host interactions of Pieris granulosis viruses." Thesis, Imperial College London, 1987. http://hdl.handle.net/10044/1/46627.
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Gunes, G. "Genome structure and instability associated with transposition in Streptomyces." Thesis, Swansea University, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.637187.
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Six IS61200-transposants, obtained by intermolecular transposition of IS6100 into the 'right-hand' chromosome end of S. lividans, and carrying amplifications and deletions were examined to investigate transposition-induced genome alterations. For this, cosmid clones containing representative regions of the chromosome ends, from two individuals genomic cosmid libraries of S. lividans and S. coelicolor were used as Southern hybridization probes. The sizes of the chromosomal amplifications, produced as a result of transposition of IS6100, were found to vary from 65.5kb to 350 kb. The nature of the telomeric sequences was further investigated, indicating that to a large extent sequences from the chromosome ends were retained in the mutants. Low-level amplifications in the 'right-hand' end were mapped to a large region extending between the terminal inverted repeat and the AUD Type 1 locus, but no concomitant large deletions were found. In parallel, isolation, cloning, and sequencing the putative terminal-DNA from S. avermitilis was attempted. Preserving the covalently attached terminal protein at the 5' end of the linear chromosome of S. avermitilis, total DNA was isolated. Restriction fragments obtained from this preparation were used for cloning. Four candidate clones obtained independently more than once were examined to check if any of them carry the chromosome end. Comparison of the DNA sequences from the four clones with another seven terminal DNA sequences revealed no similarity. However one clone, D showed 95% homology to the rho gene of S. lividans ZX7, indicating that the S. avermitilis rho gene had been cloned. The analysis of an oligonucleotide probe designed from the consensus sequence present in seven other terminal sequences. The probe generated a signal with two controls, DNA from S. lividans 1326 and ZX1 strains, whereas no signal was detected with DNA from S. avermitilis suggesting that the terminal sequence of S. avermitilis is not similar to the consensus sequence.
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Ford, Kate E. "Genome structure and genetic diversity in Crambe L. Brassicaceae." Thesis, University of East Anglia, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.327518.
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Dunning, Ted Emerson. "Finding structure in text, genome and other symbolic sequences." Thesis, University of Sheffield, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.310811.
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Coleman, Maureen Lynn. "Structure and dynamics of genome-wide diversity in Prochlorococcus." Thesis, Massachusetts Institute of Technology, 2008. http://hdl.handle.net/1721.1/43911.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Civil and Environmental Engineering, 2008.Includes bibliographical references.
The capability of microbes to thrive in myriad environments has its foundation in the diversity of microbial genomes. Here we explore adaptation and diversification through the lens of the marine cyanobacterium Prochlorococcus, which comprises a group of closely-related ecotypes that together perform most of the primary production in low-nutrient regions of the world oceans. Prochlorococcus was one of the first microbes in which a genomic basis for ecological differentiation was characterized, in the distinction between high- and low-light adapted ecotypes. It is clear, however, that other axes of differentiation are important, including temperature, nutrient availability, and biotic interactions. This thesis seeks to characterize salient aspects of genomic diversity in Prochlorococcus and to advance understanding of the ecological and evolutionary forces that shape this variation. We show that closely related isolates harbor remarkably dissimilar gene complements, and much of this variation is concentrated in specific genome regions, termed islands, that appear to have arisen through phage-mediated gene transfer. Several island-encoded genes likely play important metabolic roles, as inferred from their strong and specific upregulation under stress conditions. A region of the genome involved in phosphate assimilation has highly variable gene content that appears to reflect oceanic phosphate availability. Accordingly, we find extreme differences between strains in the transcriptional response to phosphate starvation. Using metagenomics approaches, we describe high coexisting diversity in natural Prochlorococcus populations. Nevertheless, this diversity is structured: a core genome of universal single-copy genes is augmented by a flexible genome.
(cont.) The population genome changes with water depth, reflecting genotypic variation among ecotypes and within the dominant ecotype. Finally, we show that the transcriptomes of wild Prochlorococcus correlate strongly with transcriptomes in culture as measured by microarrays. Genes of unknown function are among the most highly expressed in the wild. Several highly expressed genes show signatures of intragenic recombination, a process that likely influences their diversity and function. Overall, this work demonstrates that environmental factors such as light, temperature, nutrient availability, and interspecies interactions each leave different marks in the genome over different scales of time and space. Understanding microbial evolution requires that we dissect diversity over these multiple scales.
by Maureen Lynn Coleman.
Ph.D.
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Corless, Samuel. "Role of DNA supercoiling in genome structure and regulation." Thesis, University of Edinburgh, 2014. http://hdl.handle.net/1842/9623.
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A principle challenge of modern biology is to understand how the human genome is organised and regulated within a nucleus. The field of chromatin biology has made significant progress in characterising how protein and DNA modifications reflect transcription and replication state. Recently our lab has shown that the human genome is organised into large domains of altered DNA helical twist, called DNA supercoiling domains, similar to the regulatory domains observed in prokaryotes. In my PhD I have analysed how the maintenance and distribution of DNA supercoiling relates to biological function in human cells. DNA supercoiling domains are set up and maintained by the balanced activity of RNA transcription and topoisomerase enzymes. RNA polymerase twists the DNA, over-winding in front of the polymerase and under-winding behind. In contrast topoisomerases relieve supercoiling from the genome by introducing transient nicks (topoisomerase I) or double strand breaks (topoisomerase II) into the double helix. Topoisomerase activity is critical for cell viability, but the distribution of topoisomerase I, IIα and IIβ in the human genome is not known. Using a chromatin immunoprecipitation (ChIP) approach I have shown that topoisomerases are enriched in large chromosomal domains, with distinct topoisomerase I and topoisomerase II domains. Topoisomerase I is correlated with RNA polymerase II, genes and underwound DNA, whereas topoisomerase IIα and IIβ are associated with each other and over-wound DNA. This indicates that different topoisomerase proteins operate in distinct regions of the genome and can be independently regulated depending on the genomic environment. Transcriptional regulation by DNA supercoiling is believed to occur through changes in gene promoter structure. To investigate DNA supercoiling my lab has developed biotinylated trimethylpsoralen (bTMP) as a DNA structure probe, which preferentially intercalates into under-wound DNA. Using bTMP in conjunction with microarrays my lab identified a transcription and topoisomerase dependent peak of under-wound DNA in a meta-analysis of several hundred genes (Naughton et al. (2013)). In a similar analysis, Kouzine et al. (2013) identified an under-wound promoter structure and proposed a model of topoisomerase distribution for the regulation of promoter DNA supercoiling. To better understand the role of supercoiling and topoisomerases at gene promoters, a much larger-scale analysis of these factors was required. I have analysed the distribution of bTMP at promoters genome wide, confirming a transcription and expression dependent distribution of DNA supercoils. DNA supercoiling is distinct at CpG island and non-CpG island promoters, and I present a model in which over-wound DNA limits transcription from both CpG island promoters and repressed genes. In addition, I have mapped by ChIP topoisomerase I and IIβ at gene promoters on chromosome 11 and identified a different distribution to that proposed by Kouzine et al. (2013), with topoisomerase I maintaining DNA supercoiling at highly expressed genes. This study provides the first comprehensive analysis of DNA supercoiling at promoters and identifies the relationship between supercoiling, topoisomerase distribution and gene expression. In addition to regulating transcription, DNA supercoiling and topoisomerases are important for genome stability. Several studies have suggested a link between DNA supercoiling and instability at common fragile sites (CFSs), which are normal structures in the genome that frequently break under replication stress and cancer. bTMP was used to measure DNA supercoiling across FRA3B and FRA16D CFSs, identifying a transition to a more over-wound DNA structure under conditions that induce chromosome fragility at these regions. Furthermore, topoisomerase I, IIα and IIβ showed a pronounced depletion in the vicinity of the FRA3B and FRA16D CFSs. This provides the first experimental evidence of a role for DNA supercoiling in fragile site formation.
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Lubbe, Lizel. "Cloning and Expression of the M-Gene from the Human Coronavirus NL-63 in Different Expression Systems." Thesis, University of the Western Cape, 2008. http://etd.uwc.ac.za/index.php?module=etd&action=viewtitle&id=gen8Srv25Nme4_2721_1266364969.
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In this study, the HCoV-NL63 genome was transcribed from RNA to DNA from which the M gene was amplified with various primers designed for use in specific expression systems. The various genes were cloned into the pGEM vector and confirmed by sequencing. The genes were now expressed in cloning vectors suited for each expression system (pFastBac for baculovirus expression, pFlexi for bacterial expression and pCMV for mammalian expression). Clones were sequenced for a second time. The recombinant clone in pFlexi was expressed in KRX cells and a 36hr time course was performed. The recombinant pFastBac clone was used to infect Sf9 insect cells and P1 and P2 viral stocks were obtained. The recombinant pCMV clone was used to transfect Cos1 mammalian cells.
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Zuccolo, Andrea, John Bowers, James Estill, Zhiyong Xiong, Meizhong Luo, Aswathy Sebastian, Jose Goicoechea, et al. "A physical map for the Amborella trichopoda genome sheds light on the evolution of angiosperm genome structure." BioMed Central, 2011. http://hdl.handle.net/10150/610149.
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BACKGROUND:Recent phylogenetic analyses have identified Amborella trichopoda, an understory tree species endemic to the forests of New Caledonia, as sister to a clade including all other known flowering plant species. The Amborella genome is a unique reference for understanding the evolution of angiosperm genomes because it can serve as an outgroup to root comparative analyses. A physical map, BAC end sequences and sample shotgun sequences provide a first view of the 870 Mbp Amborella genome.RESULTS:Analysis of Amborella BAC ends sequenced from each contig suggests that the density of long terminal repeat retrotransposons is negatively correlated with that of protein coding genes. Syntenic, presumably ancestral, gene blocks were identified in comparisons of the Amborella BAC contigs and the sequenced Arabidopsis thaliana, Populus trichocarpa, Vitis vinifera and Oryza sativa genomes. Parsimony mapping of the loss of synteny corroborates previous analyses suggesting that the rate of structural change has been more rapid on lineages leading to Arabidopsis and Oryza compared with lineages leading to Populus and Vitis. The gamma paleohexiploidy event identified in the Arabidopsis, Populus and Vitis genomes is shown to have occurred after the divergence of all other known angiosperms from the lineage leading to Amborella.CONCLUSIONS:When placed in the context of a physical map, BAC end sequences representing just 5.4% of the Amborella genome have facilitated reconstruction of gene blocks that existed in the last common ancestor of all flowering plants. The Amborella genome is an invaluable reference for inferences concerning the ancestral angiosperm and subsequent genome evolution.
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McGuffin, Liam James. "Fully automated methods for protein fold recognition using predicted secondary structure." Thesis, Brunel University, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.269404.
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Kim, Yunjung. "Analysis of Multilocus Linkage Disequilibrium Structure in the Human Genome." NCSU, 2008. http://www.lib.ncsu.edu/theses/available/etd-03132008-075346/.
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The International HapMap Project and high- throughput genotyping technology have generated millions of genome-wide marker data that can be used in genetic studies. Each marker can be analyzed separately. But analyzing multiple markers simultaneously through haplotypes has generated great interest recently. Understanding the haplotype structure in the human genome may provide important information on human evolutionary history and identification of genetic variants responsible for human complex diseases. Since the alleles at closely linked markers on a single chromosome are often in statistical dependence (i.e. linkage disequilibrium (LD)), one crucial aspect of haplotype analysis is to characterize LD patterns in different regions and different populations. To assess the extent of correlation of genetic variation at multiple markers in a given region and a population, pairwise LD measures such as and have been commonly used. However, pairwise LD measures alone may be suboptimal to effectively capture the variability of background levels of disequilibrium since multilocus LD measures can provide information about simultaneous allele associations among multiple loci which pairwise LD measures miss. In addition, in order to fully characterize the haplotype structure and LD pattern at multiple markers, it is necessary to consider high order disequilibria and estimate their values.
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Granseth, Erik. "Structure, prediction, evolution and genome wide studies of membrane proteins." Doctoral thesis, Stockholm : Department of Biochemistry and Biophysics, Stockholm University, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-7027.
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Sandford, Richard N. "Studies on the structure of a novel compact vertebrate genome." Thesis, University of Cambridge, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.319320.
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Tiley, L. "Studies on the structure and function of the FMDV genome." Thesis, University of Reading, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.234358.
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Porter, Colin David. "Molluscum contagiosum virus : genome structure and mechanism of tumour genesis." Thesis, Imperial College London, 1989. http://hdl.handle.net/10044/1/47621.
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Butovskaya, Elena. "G-quadruplexes in the HIV-1 genome: structure and targeting." Doctoral thesis, Università degli studi di Padova, 2017. http://hdl.handle.net/11577/3422271.
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Nucleic acids may form non-canonical tetraplex secondary structures called G-quadruplexes. G-quadruplexes have been found in eukaryotic and prokaryotic genomes, including viruses. Located in key functional regions of genomes, G-quadruplexes play important regulatory roles in transcription, replication and translation processes. Particularly, G-quadruplex-mediated transcription regulation of oncogene promoters has been widely described.
Previous studies demonstrated that a set of dynamic G-quadruplex structures in the promoter region of the HIV-1 Long Terminal Repeat (LTR) regulates viral transcription acting as repressor elements. G-quadruplex-directed targeting with stabilizing ligands enhances their inhibitory effect, resulting in decrease of viral production and suggesting viral G4 structures as potential antiviral targets.
We aimed at 1) develop antiviral compounds selective for viral G-quadruplexes over cellular structures. We screened a newly designed series of NDI-core based G-quadruplex ligands and pointed out structural features of the compounds that led to improve the selectivity.
2) We identified by nuclear magnetic resonance the deep structural coordinates of the G-quadruplex targets as the preliminary necessary step for rational drug design approach. We described the singular hybrid quadruplex/duplex topology of the major G-quadruplex component within the LTR region, which allows novel implication for selective recognition of viral structures.
3) We also explored the formation of G-quadruplex structures at the HIV-1 RNA genome level, which emerged as a pre-integration target for the antiviral activity of a well-known G-quadruplex ligand. We investigated the formation, stability and involvement of RNA G-quadruplexes in the reverse transcription process and the role of the HIV-1 nucleocapsid protein in controlling folding of these structures.Acidi nucleici ricchi in guanine possono formare strutture secondarie alternative chiamate G-quadruplex. I G-quadruplex sono stati caratterizzati in diversi tipi di genomi, tra cui genomi virali e umano. Nel genoma umano le strutture G-quadruplex sono prinicipalmente localizzate in importanti regioni funzionali, dove possono assumere ruoli regolatori dei processi come trascrizione, replicazione a traduzione. In particolare, la regolazione della trascrizione dei promotori degli oncogeni mediata dalle strutture G-quadruplex è stata ampiamente descritta, evidenziando che i G-quadruplex promotoriali agiscono principalmente da silenziatori del processo trascrizionale. I precedenti studi, condotti dal nostro gruppo di ricerca hanno dimostrato che una serie di strutture G-quadruplex al livello del Long Terminal repeat (LTR) del genoma provirale di HIV-1 è coinvolta nella regolazione della trascrizione virale. La stabilizzazione di queste strutture con i ligandi specifici si traduce in repressione dell’attività promotoriale e in inibizione della produzione del virus in cellule infettate, suggerendo che i G-quadruplex nella regione LTR di HIV-1 possono essere dei promettenti target antivirali. Lo scopo principale di questa tesi è stato quello di individuare composti con attività antivirale che mostrano un legame preferenziale verso le strutture G-quadruplex virali. Abbiamo testato una nuova serie di composti leganti G-quadruplex sviluppata a partire dal NDI-core e abbiamo identificato dei componenti strutturali responsabili della maggiore affinità verso le strutture G-quadruplex virali che possono guidare verso ulteriore miglioramento della selettività. L’obiettivo di utilizzare un approccio razionale per lo sviluppo dei composti selettivi ha richiesto di individuare le coordinate strutturali del target. Abbiamo identificato che il componente G-quadruplex prevalente nella regione LTR considerata è foldato in una topologia molto particolare, descritta come struttura ibrida quadruplex/duplex e presenta interessanti implicazioni per il riconoscimento selettivo da parte delle piccole molecole.
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Ma, Yue. "Double-strand breaks (DSBs) and structure transition on genome-sized DNA." Thesis, https://doors.doshisha.ac.jp/opac/opac_link/bibid/BB13097333/?lang=0, 2018. https://doors.doshisha.ac.jp/opac/opac_link/bibid/BB13097333/?lang=0.
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DNA中の二本鎖切断(DSB)に対するアスコルビン酸(AA)およびDMSOの保護効果を、蛍光顕微鏡による巨大DNA(T4 DNA; 166kbp)の単分子観察によって評価した。凍結／解凍の状態に対して3つの異なる形態の放射源、可視光、γ線、および超音波の環境下にさらした。1‐プロパノールと2‐プロパノールの間で異なる効果が表れた。ゲノムDNA分子の高次構造の変化は、1−プロパノールを用いると、長軸長が濃度60％で最小を示し、次にアルコール含有量の増加と共に増加する傾向があることを見出した。一方、2−プロパノールを用いると、長軸長はアルコール含有量の増加と共にほぼ単調な減少を示した。The protective effect of ascorbic acid (AA) and DMSO against double-strand breaks (DSBs) in DNA was evaluated by single-molecule observation of giant DNA (T4 DNA; 166kbp) through fluorescence microscopy. Samples were exposed to three different forms of radiation: visible light, γ-ray, and ultrasound or freeze/thawing. The change of the higher-order structure of genomic DNA molecules in the presence of alcohols by use of single DNA observation with fluorescence microscopy, by focusing our attention to unveil the different effect between 1-propanol and 2-propanol.
博士(工学)
Doctor of Philosophy in Engineering
同志社大学
Doshisha University
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Chambers, Emily Victoria. "Conservation and divergence in higher order chromatin structure." Thesis, University of Edinburgh, 2013. http://hdl.handle.net/1842/8803.
Full textAbstract:
Aspects of higher order chromatin structure such as replication timing, lamina association and Hi-C inter-locus interactions have been recently studied in several human and mouse cell types and it has been suggested that most of these features of genome organisation are conserved over evolution. However, the extent of evolutionary divergence in higher order structure has not been rigorously measured across the mammalian genome, and little is known about the characteristics of any divergent loci defined. Here we generate an orthologous dataset combining multiple measurements of chromatin structure and organisation over many embryonic cell types for both human and mouse that, for the first time, allows a comprehensive assessment of the extent of structural divergence between different mammalian genomes. Comparison of orthologous regions confirms that all measurable facets of higher order structure are conserved between human and mouse, across the majority of the orthologous genome. This broad similarity is observed in spite of the substantial time since the species diverged, differences in experimental procedures among the datasets examined, and the presence of cell type specific structures at many loci. However, we also identify hundreds of regions showing consistent evidence of divergence between these species, constituting at least 10% of the orthologous mammalian genome and encompassing many hundreds of human and mouse genes. Divergent regions are enriched in genes implicated in vertebrate development, suggesting important roles for structural divergence in mammalian evolution. They are also relatively enriched for genes showing divergent expression patterns between human and mouse ES cells, implying these regions may underlie divergent regulation. Divergent regions show unusual shifts in compositional bias, sequence divergence and are unevenly distributed across both genomes. We investigate the mechanisms of divergence in higher order structure by examining the influence of sequence divergence and also many features of primary level chromatin, such as histone modification and DNA methylation patterns. Using multiple regression, we identify the dominant factors that appear to have shaped the physical structure of the mammalian genome. These data suggest that, though relatively rare, divergence in higher order chromatin structure has played important roles during evolution.
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Spriggs, Ruth Verity. "Development of the ASSAM and ASPROTE programs for protein tertiary structure searching." Thesis, University of Sheffield, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.269377.
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Dabbagh, Nadja [Verfasser]. "Chloroplast Genome Diversity in the Phototrophic Euglenoids, with Emphasis on Genome Structure, Synteny and Intron Evolution / Nadja Dabbagh." Wuppertal : Universitätsbibliothek Wuppertal, 2017. http://d-nb.info/1148444106/34.
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Dabbagh, Nadja Alice Faride [Verfasser]. "Chloroplast Genome Diversity in the Phototrophic Euglenoids, with Emphasis on Genome Structure, Synteny and Intron Evolution / Nadja Dabbagh." Wuppertal : Universitätsbibliothek Wuppertal, 2017. http://d-nb.info/1148444106/34.
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Woodward, Jessica Christina. "Cell-lineage-specific chromosomal instability in condensin II mutant mice." Thesis, University of Edinburgh, 2016. http://hdl.handle.net/1842/22921.
Full textAbstract:
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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Foster, Gary D. "The structure and expression of the genome of potato virus S." Thesis, Queen's University Belfast, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.335333.
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Fontaine, Jean-Marc. "Structure et evolution du genome mitochondrial de l'algue brune pylaiella littoralis." Paris 6, 1996. http://www.theses.fr/1996PA066146.
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Le genome mitochondrial de pylaiella littoralis est un genome circulaire de taille moyenne, 58 kbp. Le sequencage systematique de chaque clone representatif de ce genome a permis d'etablir une carte genomique presque complete, d'identifier une cinquantaine de genes, et de localiser la presence de zones promotrices putatives de type eubacterien a facteur -70. La phylogenie du gene 23s a ete etudie, ceci par la realisation de la structure secondaire et de l'alignement de sa sequence avec celles de genes homologues provenant d'autres organismes. Les resultats montrent que ce gene est plus proche de ceux des proteobacteries que ceux des autres organismes. Un total de quatre introns de groupe iib a ete identifie dans le gene specifiant l'arn 23s et de trois introns de groupe iia dans le gene specifiant le coxi. Ces introns sont des arns autocatalytiques, c'est a dire ayant la possibilite de s'autoepisser in vitro. Certains de ces introns peuvent posseder des phases de lecture ouverte (orfs) apparentees a des transcriptases inverses (ti). Des etudes phylogenetiques fondees d'une part sur les orfs des introns de groupe iib et d'autre part sur les orfs des introns de groupe iia montrent que les deux premiers introns du 23s semblent avoir un ancetre commun avec un intron present dans les cyanobacteries et les plastes, et de facon surprenante, sont moins proches de ceux des mitochondries de levures et de marchantia polymorpha. Au contraire les ti contenues dans les trois introns du gene coxi sont proches des ti de tous les introns mitochondriaux connus. Nous avons montres que ces orf coevoluent avec les introns et appartiennent a deux lignees differentes. Nous discutons egalement de l'origine de ces introns. Des experiences d'autoepissage in vitro pour certains de ces introns ont permis d'observer une forte activite d'autoepissage a tres basse concentration en mgcl#2, ce qui constitue le premier exemple d'autoepissage se rapprochant des conditions physiologiques. En resume il semble que cette molecule ait conserve des caracteristiques plus primitives que les autres genomes mitochondriaux etudies. Ces resultats sont discutes dans le cadre de la theorie endosymbiotique sur l'origine et l'evolution des mitochondries
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Lahbib, Mansais Yvette. "Structure et expression du genome du bacteriophagetempere mv4 de lactobacillus bulgaricus." Toulouse 3, 1989. http://www.theses.fr/1989TOU30093.
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Caracterisation moleculaire du bacteriophage mv4 de lactobacillus bulgaricus. Realisation d'une carte physique du genome. Clonage de l'adn du phage et etude de l'expression des genes clones. Des genes codant pour des proteines de structure et une lysine ont pu etre localises. Mise en evidence du site d'integration du phage dans le chromosome de souches lysogenes de lactobacillus. Etude comparative du phage mv4 avec 3 autres phages temperes et 4 phages virulents
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Iseric, Hamza. "BISER: fast characterization of segmental duplication structure in multiple genome assemblies." Thesis, Schloss Dagstuhl -- Leibniz-Zentrum für Informatik, 2021. http://hdl.handle.net/1828/13343.
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The increasing availability of high-quality genome assemblies raised interest in the characterization of genomic architecture. Major architectural elements, such as common repeats and segmental duplications (SDs), increase genome plasticity that stimulates further evolution by changing the genomic structure and inventing new genes. Optimal computation of SDs within a genome requires quadratic-time local alignment algorithms that are impractical due to the size of most genomes. Additionally, to perform evolutionary analysis, one needs to characterize SDs in multiple genomes and find relations between those SDs and unique (non-duplicated) segments in other genomes. A na ̈ıve approach consisting of multiple sequence alignment would make the optimal solution to this problem even more impractical. Thus there is a need for fast and accurate algorithms to characterize SD structure in multiple genome assemblies to better understand the evolutionary forces that shaped the genomes of today. Here we introduce a new approach, BISER, to quickly detect SDs in multiple genomes and identify elementary SDs and core duplicons that drive the formation of such SDs. BISER improves earlier tools by (i) scaling the detection of SDs with low homology (75%) to multiple genomes while introducing further 10–34× speed-ups over the existing tools, and by (ii) characterizing elementary SDs and detecting core duplicons to help trace the evolutionary history of duplications to as far as 300 million years.Graduate
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Hart, Christopher Edward Simon Melvin I. "Inferring genetic regulatory network structure: integrative analysis of genome-scale data /." Diss., Pasadena, Calif. : California Institute of Technology, 2005. http://resolver.caltech.edu/CaltechETD:etd-03152005-110423.
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Breen, James. "Assembly of a Complex Genome: Defining Elements of Structure and Function." Thesis, Breen, James (2009) Assembly of a Complex Genome: Defining Elements of Structure and Function. PhD thesis, Murdoch University, 2009. https://researchrepository.murdoch.edu.au/id/eprint/2990/.
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The post-human genome sequencing project era has seen an influx of genome sequencing projects established to investigate the structure, composition and characteristics of plant genomes. While the genome sequences of smaller plant genomes (ie. Rice) are currently available, there has been a lack of progress on the study of large, complex genomes such as barley (Hordeum vulgare) and wheat (Triticum aestivum), due to the difficulties in their sequencing and assembly. The aim of this study is to assemble and annotate targeted regions of chromosome 3B from Triticum aestivum cv. Chinese Spring (CS) and Hope. This study also aimed to complete a comprehensive, inter- and intra-species comparative analysis using Bioinformatics tools and strategies, in order to define structural and functional elements within the genome.
Genome sequences totalling 2.7Mb from two different loci of chromosome 3B in two different cultivars (ctg11 from the short arm of CS, ctg1034 from the long arm of CS and three assembled sequences over the equivalent ctg11 region of Hope) were assembled using a novel ‘two-phase’ process that integrated information from a genome sequence assembler and a Triticeae-specific transposable element database. Through comparative genomics analysis a gene island was identified within a highly repetitive, heterochromatic region on 3BL that was highly conserved over four other cereal genomes (Brachypodium distachyon, Oryza sativa, Sorghum bicolor and Zea mays). Chromodomain-containing long terminal repeats from the gypsy family of retrotransposons were identified adjacent to the gene island and may suggest an involvement in the targeted insertion of transposable elements at the loci, protecting the gene-island from dynamic evolutionary change. Characterisation of the ctg11 (Sr2 region) genome sequence on 3BS, identified a large ~60kb mitochondrial genome insert and three members of the multi-gene beta-expansin family, with sequence analysis indicating local duplication within the sequence and rearrangements when compared to the equivalent region in a different wheat cultivar. In silico and real-time transcription analysis of the individual gene was also confirmed. Within the equivalent ctg11 in Hope, a germin-like protein (GLP) cluster was identified and characterised that distinguishes between the two wheat cultivars. The genes in this GLP cluster were identified to belong to a sub-gene family that conferred broad level basal resistance in transient over-expressed systems in rice and barley.
The main outcome of this study was the development of a novel strategy of genome sequence assembly by utilising the complex component of the wheat genome that made assembly difficult: transposable elements. The complex genome sequence assembly methodology outlined in this thesis is suitable to be used as a model for future sequence assembly studies. The assembly of large pseudomolecule sequences (among the largest and most complete ever assembled in the wheat genome) enabled the Bioinformatics analysis of a representative sample of wheat chromosome 3B, providing valuable in silico outputs for future functional analyses and allowing an in-depth intra- and inter-species comparative analysis with related genomes.
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Zhao, Zhiyu. "Robust and Efficient Algorithms for Protein 3-D Structure Alignment and Genome Sequence Comparison." ScholarWorks@UNO, 2008. http://scholarworks.uno.edu/td/851.
Full textAbstract:
Sequence analysis and structure analysis are two of the fundamental areas of bioinformatics research. This dissertation discusses, specifically, protein structure related problems including protein structure alignment and query, and genome sequence related problems including haplotype reconstruction and genome rearrangement. It first presents an algorithm for pairwise protein structure alignment that is tested with structures from the Protein Data Bank (PDB). In many cases it outperforms two other well-known algorithms, DaliLite and CE. The preliminary algorithm is a graph-theory based approach, which uses the concept of \stars" to reduce the complexity of clique-finding algorithms. The algorithm is then improved by introducing \double-center stars" in the graph and applying a self-learning strategy. The updated algorithm is tested with a much larger set of protein structures and shown to be an improvement in accuracy, especially in cases of weak similarity. A protein structure query algorithm is designed to search for similar structures in the PDB, using the improved alignment algorithm. It is compared with SSM and shows better performance with lower maximum and average Q-score for missing proteins. An interesting problem dealing with the calculation of the diameter of a 3-D sequence of points arose and its connection to the sublinear time computation is discussed. The diameter calculation of a 3-D sequence is approximated by a series of sublinear time deterministic, zero-error and bounded-error randomized algorithms and we have obtained a series of separations about the power of sublinear time computations. This dissertation also discusses two genome sequence related problems. A probabilistic model is proposed for reconstructing haplotypes from SNP matrices with incomplete and inconsistent errors. The experiments with simulated data show both high accuracy and speed, conforming to the theoretically provable e ciency and accuracy of the algorithm. Finally, a genome rearrangement problem is studied. The concept of non-breaking similarity is introduced. Approximating the exemplar non-breaking similarity to factor n1..f is proven to be NP-hard. Interestingly, for several practical cases, several polynomial time algorithms are presented.
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Kibler, Tracey Deborah. "A computational characterisation of the relationship between genome structure and disease genes." Thesis, University of the Western Cape, 2012. http://hdl.handle.net/11394/4509.
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>Magister Scientiae - MScThis is a pilot study to investigate the relationship between disease gene status and the structure of the human genome with specific reference to regions of recombination. It compares certain characteristics of a control set of genes, with no reported association or function in any known disease, with a second set of well-curated genes with a known association to a disease. One of the benefits of recombination is the introduction of new combinations of genetic variation in the genome. Recombination hotspots are regions on the chromosome where higher than normal frequencies of breaking and rejoining between homologous chromosomes occur during meiosis. The hotspot regions exhibit both a non-random distribution across the human genome and varying frequencies of breaking and rejoining. The study analyzed a set of features that represent general properties of human genes; namely base composition (percentage GC content), genetic variation (single nucleotide polymorphisms - SNPs), gene length, and positional effect (distance from chromosome end), in both the disease-associated gene set and the control set. These features were linked to recombination hotspots in the human genome and the frequency of recombination at these hotspots. Descriptive statistics was used to determine differences between the occurrences of these features in disease-associated genes compared to the control set, as well as differences in the occurrence of these same features in subset of genes containing an internal recombination hotspot compared to the genes with no internal recombination hotspot. The study found that disease-associated genes are generally longer than those in the control set, which is consistent with previous studies. It also found that disease-associated genes are much more likely to contain a recombination hotspot than those genes with no disease association. The study did not, however, find any association between disease gene status and the other set of features; namely GC content, SNP numbers or the position of a gene on the chromosome. Further analysis of the data suggested that the increased probability of disease-associated genes containing a recombination hotspot is most likely an effect of longer gene length and that the presence of a recombination hotspot is not sufficient in its own right to cause disease gene status.
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Li, Jianjian. "Molecular and Cytogenetical Dissection of the Rye (Secale cereale L.) Genome Structure." Kyoto University, 2013. http://hdl.handle.net/2433/180631.
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Kyoto University (京都大学)0048
新制・課程博士
博士(農学)
甲第17963号
農博第2031号
新制||農||1018(附属図書館)
学位論文||H25||N4807(農学部図書室)
30793
京都大学大学院農学研究科応用生物科学専攻
(主査)教授 遠藤 隆, 准教授 河原 太八, 教授 奥本 裕
学位規則第4条第1項該当
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Yu, Michael Ku. "Structure-based realignment of non-coding RNAs in multiple whole genome alignments." Thesis, Massachusetts Institute of Technology, 2011. http://hdl.handle.net/1721.1/66817.
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Thesis (M. Eng.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2011.Cataloged from PDF version of thesis.
Includes bibliographical references (p. 62-65).
Whole genome alignments have become a central tool in biological sequence analysis. A major application is the de novo prediction of non-coding RNAs (ncRNAs) from structural conservation visible in the alignment. However, current methods for constructing genome alignments do so by explicitly optimizing for sequence similarity but not structural similarity. Therefore, de novo prediction of ncRNAs with high structural but low sequence conservation is intrinsically challenging in a genome alignment because the conservation signal is typically hidden. This study addresses this problem with a method for genome-wide realignment of potential ncRNAs according to structural similarity. Doing so reveals thousands of new high-confidence ncRNA predictions with particularly low sequence conservation from an alignment of 12 Drosophila genomes and hundreds from an alignment of 28 vertebrate genomes in the Encode project.
by Michael Ku Yu.
M.Eng.
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Hafeez, Farah. "Study of genome structure and organization of oil palm (Elaeis guineensis, Jacq.)." Thesis, University of Cambridge, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.613880.
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Bratcher, Holly Bea. "Meningococcal genome dynamics : an allele based, population approach to define lineage structure." Thesis, University of Oxford, 2015. https://ora.ox.ac.uk/objects/uuid:08db20f8-2bda-4322-a6bc-5745139bbbad.
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Advances in genome sequencing technologies have rapidly expanded the number of bacterial genome sequences available for study, permitting the emergence of the discipline of population genomics. Bioinformatics platforms were used to exploit this resource by the provision of data in an easily accessible and uniform format. The de novo assembly, combined with gene-by-gene annotation, generated high quality draft genomes in which the majority of protein-encoding genes were present with high accuracy. The approach catalogued diversity efficiently and was a practical approach to interpreting whole genome sequence data for a large bacterial population. The hyperinvasive meningococcal Lineage 3 core and accessory genome was described and mobile genetic elements and undescribed proteins were found to be influencing the shape of the lineages evolution and population structure. Commensal carriage of the meningococcus was examined using temporally paired isolates. Long-term carriage was found and the comparison of the genomes pairs found a highly conserved set of core genes. The methods used generated novel insights into the biology of the meningococcus and improved our understanding of the whole population structure, not just disease causing lineages. This work contributes to knowledge of genomic evolution of bacteria and population structure within a species.
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Zamudio, Alicia V. (Alicia Viridiana Zamudio Monters de Oca). "Insights into gene regulation by genome structure, phase separation and developmental signaling." Thesis, Massachusetts Institute of Technology, 2020. https://hdl.handle.net/1721.1/128064.
Full textAbstract:
Thesis: Ph. D., Massachusetts Institute of Technology, Department of Biology, 2020Cataloged from PDF of thesis.
Includes bibliographical references.
Proper regulation of gene expression is essential to the developmental processes that give rise to hundreds of different cell types with unique cellular identities. Regulation of protein-coding and long non-coding RNA genes by RNA polymerase II is carried out by the coordinated action of transcription factors and cofactors. Transcription factors can be cell-type specific and bind cell-type specific gene regulatory regions called enhancers, which can be located far upstream or downstream from the gene they activate. The enhancer-bound factors can loop to the promoters of cell-type specific genes to enhance the levels of transcription of these genes, and studies described in this thesis have provided new insights into the factors that contribute to this looping process (Weintraub et al., 2017). Recent studies have revealed that super-enhancers, which contribute to regulation of genes with prominent roles in cell identity, form phase-separated condensates that compartmentalize and concentrate the transcription apparatus at these genes. This insight led us to test the idea that signaling factors, which bring information regarding the developmental environment of cells to the transcription apparatus, might preferentially interact with super-enhancers through condensate interactions that were not considered in previous studies of signaling. Our studies confirmed that super-enhancer condensate do indeed facilitate the preferential localization of signaling factors to genes with prominent roles in cell identity (Zamudio et al., 2019). Thus, the studies described in this thesis provide new insights into gene regulation by genome structuring, phase separation and developmental signaling.
by Alicia V. Zamudio.
Ph. D.
Ph.D. Massachusetts Institute of Technology, Department of Biology
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Ravel, Christophe. "Structure et dynamique du génome de Leishmania (protozoa, kinetoplastida)." Montpellier 1, 1996. http://www.theses.fr/1996MON1T004.
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Pu, Ting. "Genome characterization and population genetic structure of white pine blister rust, Cronartium ribicola." Thesis, University of British Columbia, 2014. http://hdl.handle.net/2429/51700.
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Rust fungi cause some of the most severe pine diseases. Cronartium ribicola (J. C. Fisch.), the causal agent of white pine blister rust, was introduced accidentally to North America from Europe in the late 1800s. Since then, it has devastated a large number of native, commercially valuable white pines, and is threatening alpine ecosystem stability by endangering high elevation white pines. In order to better understand the global epidemiology of this pathogen, we conducted a genome scan of a global collection of C. ribicola using Genotyping-by-Sequencing (GBS) to: 1) ascertain the origin and the routes of introduction of C. ribicola, and 2) uncover cryptic population structure of C. ribicola in western North America, in relation to different pine hosts, climates and landscapes. More than eight thousand single nucleotide polymorphism markers were genotyped on 192 samples of C. ribicola from three continents. The highest genetic and nucleotidic diversity were observed in Siberian samples, supporting the hypothesis that central Russia is the center of origin of C. ribicola. Diversity was reduced in all other populations and was lowest in western North America. Genetic and nucleotidic diversity were two to five times lower in western than in eastern North America. This result supports the observation of multiple introductions of the pathogen in eastern North America and contrasts with the single reported introduction in western North America. However, western populations had a larger number of rare alleles. This could represent the signature of population expansion following a bottleneck or a selective sweep. A cryptic Coast/Interior split was detected within the western cluster, most likely maintained by the scarcity of white pines in central British Columbia acting like a barrier to gene flow. Finally, western individuals with a high level of eastern admixture were discovered in two populations east of the Continental Divide. This could indicate that the eastern-western barrier to gene flow is leaky. Such information is of significance to white pine resistance breeding programs and to the monitoring of this disease.Forestry, Faculty of
Graduate
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Beeharry, Yasnee. "Role of RNA Genome Structure and Paraspeckle Proteins In Hepatitis Delta Virus Replication." Thesis, Université d'Ottawa / University of Ottawa, 2016. http://hdl.handle.net/10393/35343.
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The Hepatitis Delta Virus (HDV) is an RNA pathogen that uses the host DNA-dependent RNA polymerase II (RNAP II) to replicate. Previous studies identified the right terminal domain of genomic polarity (R199G) of HDV RNA as an RNAP II promoter, but the features required for HDV RNA to be used as an RNA promoter were unknown. In order to identify the structural features of an HDV RNA promoter, I analyzed 473,139 sequences representing 2,351 new R199G variants generated by high-throughput sequencing of a viral population replicating in 293 cells. To complement this analysis, I also analyzed the same region from HDV sequences isolated from various hosts. Base pair covariation analysis indicates a strong
selection for the rod-like conformation. Several selected RNA motifs were identified,
including a GC-rich stem, a CUC/GAG motif and a uridine at the initiation site of
transcription. In addition, a polarization of purine/pyrimidine content was identified, which might represent a motif favourable for the binding of the host Polypyrimidine tract-binding protein-associated-splicing-factor (PSF), p54 and Paraspeckle Protein 1 (PSP1). Previously, it was shown that R199G binds both RNAP II and PSF, that PSF increased the HDV levels during in vitro transcription and that p54 binds R199G. In the present study, I showed that PSP1 also associates with HDV RNA and I investigated whether these proteins are required for HDV replication. My results show that knockdown of PSF, p54 and PSP1 resulted in a decrease of HDV accumulation. These proteins are highly concentrated in paraspeckles, which are nuclear structures involved in storage of transcripts generated by RNAP II. I found that upon viral replication in 293 cells, PSP1 appeared as bigger foci present outside of the
nucleus, while PSF and p54 foci remained in the nucleus. NEAT1 is a long non-coding RNA essential for the formation of paraspeckles. Upon HDV replication, I found an increase of the intensity and size of NEAT1 foci that correlates with an increase of NEAT1 transcripts. Altogether, these data suggest that HDV replication results in an alteration of the paraspeckles structures, providing foundation for further investigation of the paraspeckles role in HDV cycle. Overall, the present study addresses the importance of the HDV RNA structure and of the host paraspeckle proteins for HDV replication.
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Bland, Michael Jason. "Study of the constraints sustaining the two chromosome genome structure of vibrio cholerae." Paris 6, 2013. http://www.theses.fr/2013PA066794.
Full textAbstract:
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 genomeLa 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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Harwood, Janet C. "Defining the chromatin structure of the human genome using size-selected nucleosome mapping." Thesis, Cardiff University, 2015. http://orca.cf.ac.uk/89692/.
Full textAbstract:
The work in this thesis examines genome-wide and local changes in the patterns of nucleosome positioning throughout the human genome. Nucleosomes are the fundamental repeating unit of chromatin. Their properties and positioning in the genome dictate whether and how proteins involved in gene regulation can access DNA. Nucleosomes are dynamic; their positions can vary considerably at some loci from one cell type to another. Chromatin remodelling complexes can change the structure and the positions of nucleosomes. Their mis-regulation leads to congenital defects affecting pre-natal and early childhood development and is associated with neuro-psychiatric disorders. As mutations in genes that encode chromatin remodelling proteins are associated with human mental health disorders, the work in this thesis focusses on changes that occur in chromatin structure during early neural development. I have used MNase-seq data to construct genome-wide, high-resolution chromatin particle positioning maps from undifferentiated human induced pluripotent stem cells (hiPSC) and following differentiation to the neuro-progenitor cell (NPC) stage. These maps reveal that a small proportion of the pluripotent genome possesses well-positioned nucleosomes, the number of which increases approximately 8-fold during neural cell development. This is accompanied by changes in the distribution and localisation of nucleosomes between iPS and NPC cells. Differences in nucleosome positioning during neural cell differentiation were investigated at regulatory regions. Loss and gain of positioned nucleosomes at TSS of pluripotent and neural-specific genes was detected and correlated with gene expression. In addition I investigated the chromatin structure at the binding motifs of two important genome regulators REST and CTCF in detail. Nucleosome positioning is maintained at REST binding motifs during neural cell development. In contrast, at CTCF sites nucleosome repositioning occurs during neural cell development. This work provides insight into the role of chromatin structure in the regulation of human neural cell differentiation.