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Journal articles on the topic 'Genome spatial organization'

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Published: 7 July 2024
Last updated: 7 July 2024

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1

Parada, L. "Spatial genome organization." Experimental Cell Research 296, no. 1 (May 15, 2004): 64–70. http://dx.doi.org/10.1016/j.yexcr.2004.03.013.

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2

Rajarajan, Prashanth, Sergio Espeso Gil, Kristen J. Brennand, and Schahram Akbarian. "Spatial genome organization and cognition." Nature Reviews Neuroscience 17, no. 11 (October 6, 2016): 681–91. http://dx.doi.org/10.1038/nrn.2016.124.

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3

Brickner, Jason. "Genetic and epigenetic control of the spatial organization of the genome." Molecular Biology of the Cell 28, no. 3 (February 2017): 364–69. http://dx.doi.org/10.1091/mbc.e16-03-0149.

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Eukaryotic genomes are spatially organized within the nucleus by chromosome folding, interchromosomal contacts, and interaction with nuclear structures. This spatial organization is observed in diverse organisms and both reflects and contributes to gene expression and differentiation. This leads to the notion that the arrangement of the genome within the nucleus has been shaped and conserved through evolutionary processes and likely plays an adaptive function. Both DNA-binding proteins and changes in chromatin structure influence the positioning of genes and larger domains within the nucleus. This suggests that the spatial organization of the genome can be genetically encoded by binding sites for DNA-binding proteins and can also involve changes in chromatin structure, potentially through nongenetic mechanisms. Here I briefly discuss the results that support these ideas and their implications for how genomes encode spatial organization.
4

Finn, Elizabeth H., and Tom Misteli. "Molecular basis and biological function of variability in spatial genome organization." Science 365, no. 6457 (September 5, 2019): eaaw9498. http://dx.doi.org/10.1126/science.aaw9498.

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The complex three-dimensional organization of genomes in the cell nucleus arises from a wide range of architectural features including DNA loops, chromatin domains, and higher-order compartments. Although these features are universally present in most cell types and tissues, recent single-cell biochemistry and imaging approaches have demonstrated stochasticity in transcription and high variability of chromatin architecture in individual cells. We review the occurrence, mechanistic basis, and functional implications of stochasticity in genome organization. We summarize recent observations on cell- and allele-specific variability of genome architecture, discuss the nature of extrinsic and intrinsic sources of variability in genome organization, and highlight potential implications of structural heterogeneity for genome function.
5

Xie, Ting, Liang-Yu Fu, Qing-Yong Yang, Heng Xiong, Hongrui Xu, Bin-Guang Ma, and Hong-Yu Zhang. "Spatial features for Escherichia coli genome organization." BMC Genomics 16, no. 1 (2015): 37. http://dx.doi.org/10.1186/s12864-015-1258-1.

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6

Kim, S. H., P. G. McQueen, M. K. Lichtman, E. M. Shevach, L. A. Parada, and T. Misteli. "Spatial genome organization during T-cell differentiation." Cytogenetic and Genome Research 105, no. 2-4 (2004): 292–301. http://dx.doi.org/10.1159/000078201.

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7

Ramani, Vijay, Jay Shendure, and Zhijun Duan. "Understanding Spatial Genome Organization: Methods and Insights." Genomics, Proteomics & Bioinformatics 14, no. 1 (February 2016): 7–20. http://dx.doi.org/10.1016/j.gpb.2016.01.002.

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8

Bickmore, Wendy A. "The Spatial Organization of the Human Genome." Annual Review of Genomics and Human Genetics 14, no. 1 (August 31, 2013): 67–84. http://dx.doi.org/10.1146/annurev-genom-091212-153515.

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9

Purugganan, Michael D. "Scale-invariant spatial patterns in genome organization." Physics Letters A 175, no. 3-4 (April 1993): 252–56. http://dx.doi.org/10.1016/0375-9601(93)90836-o.

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10

Llorens-Giralt, Palmira, Carlos Camilleri-Robles, Montserrat Corominas, and Paula Climent-Cantó. "Chromatin Organization and Function in Drosophila." Cells 10, no. 9 (September 8, 2021): 2362. http://dx.doi.org/10.3390/cells10092362.

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Eukaryotic genomes are packaged into high-order chromatin structures organized in discrete territories inside the cell nucleus, which is surrounded by the nuclear envelope acting as a barrier. This chromatin organization is complex and dynamic and, thus, determining the spatial and temporal distribution and folding of chromosomes within the nucleus is critical for understanding the role of chromatin topology in genome function. Primarily focusing on the regulation of gene expression, we review here how the genome of Drosophila melanogaster is organized into the cell nucleus, from small scale histone–DNA interactions to chromosome and lamina interactions in the nuclear space.
11

Finn, Elizabeth H., Gianluca Pegoraro, Hugo B. Brandão, Anne-Laure Valton, Marlies E. Oomen, Job Dekker, Leonid Mirny, and Tom Misteli. "Extensive Heterogeneity and Intrinsic Variation in Spatial Genome Organization." Cell 176, no. 6 (March 2019): 1502–15. http://dx.doi.org/10.1016/j.cell.2019.01.020.

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12

Pederson, Thoru. "The spatial organization of the genome in mammalian cells." Current Opinion in Genetics & Development 14, no. 2 (April 2004): 203–9. http://dx.doi.org/10.1016/j.gde.2004.02.008.

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13

Meaburn, Karen J., Tom Misteli, and Evi Soutoglou. "Spatial genome organization in the formation of chromosomal translocations." Seminars in Cancer Biology 17, no. 1 (February 2007): 80–90. http://dx.doi.org/10.1016/j.semcancer.2006.10.008.

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14

Alber, Frank. "101 Exploring the 3D spatial organization of the genome." Journal of Biomolecular Structure and Dynamics 31, sup1 (January 2013): 64. http://dx.doi.org/10.1080/07391102.2013.786343.

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15

Joffe, Boris, Heinrich Leonhardt, and Irina Solovei. "Differentiation and large scale spatial organization of the genome." Current Opinion in Genetics & Development 20, no. 5 (October 2010): 562–69. http://dx.doi.org/10.1016/j.gde.2010.05.009.

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16

Tjong, Harianto, Wenyuan Li, Reza Kalhor, Chao Dai, Shengli Hao, Ke Gong, Yonggang Zhou, et al. "Population-based 3D genome structure analysis reveals driving forces in spatial genome organization." Proceedings of the National Academy of Sciences 113, no. 12 (March 7, 2016): E1663—E1672. http://dx.doi.org/10.1073/pnas.1512577113.

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Conformation capture technologies (e.g., Hi-C) chart physical interactions between chromatin regions on a genome-wide scale. However, the structural variability of the genome between cells poses a great challenge to interpreting ensemble-averaged Hi-C data, particularly for long-range and interchromosomal interactions. Here, we present a probabilistic approach for deconvoluting Hi-C data into a model population of distinct diploid 3D genome structures, which facilitates the detection of chromatin interactions likely to co-occur in individual cells. Our approach incorporates the stochastic nature of chromosome conformations and allows a detailed analysis of alternative chromatin structure states. For example, we predict and experimentally confirm the presence of large centromere clusters with distinct chromosome compositions varying between individual cells. The stability of these clusters varies greatly with their chromosome identities. We show that these chromosome-specific clusters can play a key role in the overall chromosome positioning in the nucleus and stabilizing specific chromatin interactions. By explicitly considering genome structural variability, our population-based method provides an important tool for revealing novel insights into the key factors shaping the spatial genome organization.
17

Ohno, Masae, David G. Priest, and Yuichi Taniguchi. "Nucleosome-level 3D organization of the genome." Biochemical Society Transactions 46, no. 3 (April 6, 2018): 491–501. http://dx.doi.org/10.1042/bst20170388.

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Nucleosomes are the unitary structures of chromosome folding, and their arrangements are intimately coupled to the regulation of genome activities. Conventionally, structural analyses using electron microscopy and X-ray crystallography have been used to study such spatial nucleosome arrangements. In contrast, recent improvements in the resolution of sequencing-based methods allowed investigation of nucleosome arrangements separately at each genomic locus, enabling exploration of gene-dependent regulation mechanisms. Here, we review recent studies on nucleosome folding in chromosomes from these two methodological perspectives: conventional structural analyses and DNA sequencing, and discuss their implications for future research.
18

Junaid, Alim, Baljinder Singh, and Sabhyata Bhatia. "Evolutionary insights into 3D genome organization and epigenetic landscape ofVigna mungo." Life Science Alliance 7, no. 1 (November 3, 2023): e202302074. http://dx.doi.org/10.26508/lsa.202302074.

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Eukaryotic genomes show an intricate three-dimensional (3D) organization within the nucleus that regulates multiple biological processes including gene expression. Contrary to animals, understanding of 3D genome organization in plants remains at a nascent stage. Here, we investigate the evolution of 3D chromatin architecture in legumes. By using cutting-edge PacBio, Illumina, and Hi-C contact reads, we report a gap-free, chromosome-scale reference genome assembly ofVigna mungo, an important minor legume cultivated in Southeast Asia. We spatially resolvedV. mungochromosomes into euchromatic, transcriptionally active A compartment and heterochromatic, transcriptionally-dormant B compartment. We report the presence of TAD-like-regions throughout the diagonal of the HiC matrix that resembled transcriptional quiescent centers based on their genomic and epigenomic features. We observed high syntenic breakpoints but also high coverage of syntenic sequences and conserved blocks in boundary regions than in the TAD-like region domains. Our findings present unprecedented evolutionary insights into spatial 3D genome organization and epigenetic patterns and their interaction within theV. mungogenome. This will aid future genomics and epigenomics research and breeding programs ofV. mungo.
19

Stanic, Mia, and Karim Mekhail. "Integration of DNA damage responses with dynamic spatial genome organization." Trends in Genetics 38, no. 3 (March 2022): 290–304. http://dx.doi.org/10.1016/j.tig.2021.08.016.

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20

Fujita, Yuki, and Toshihide Yamashita. "Spatial organization of genome architecture in neuronal development and disease." Neurochemistry International 119 (October 2018): 49–56. http://dx.doi.org/10.1016/j.neuint.2017.06.014.

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21

Nicodemi, Mario, and Antonella Prisco. "Thermodynamic Pathways to Genome Spatial Organization in the Cell Nucleus." Biophysical Journal 96, no. 6 (March 2009): 2168–77. http://dx.doi.org/10.1016/j.bpj.2008.12.3919.

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22

O'Sullivan, J. M., D. M. Sontam, R. Grierson, and B. Jones. "Repeated elements coordinate the spatial organization of the yeast genome." Yeast 26, no. 2 (February 2006): 125–38. http://dx.doi.org/10.1002/yea.1657.

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23

Chen, Yu, Yang Zhang, Yuchuan Wang, Liguo Zhang, Eva K. Brinkman, Stephen A. Adam, Robert Goldman, Bas van Steensel, Jian Ma, and Andrew S. Belmont. "Mapping 3D genome organization relative to nuclear compartments using TSA-Seq as a cytological ruler." Journal of Cell Biology 217, no. 11 (August 28, 2018): 4025–48. http://dx.doi.org/10.1083/jcb.201807108.

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While nuclear compartmentalization is an essential feature of three-dimensional genome organization, no genomic method exists for measuring chromosome distances to defined nuclear structures. In this study, we describe TSA-Seq, a new mapping method capable of providing a “cytological ruler” for estimating mean chromosomal distances from nuclear speckles genome-wide and for predicting several Mbp chromosome trajectories between nuclear compartments without sophisticated computational modeling. Ensemble-averaged results in K562 cells reveal a clear nuclear lamina to speckle axis correlated with a striking spatial gradient in genome activity. This gradient represents a convolution of multiple spatially separated nuclear domains including two types of transcription “hot zones.” Transcription hot zones protruding furthest into the nuclear interior and positioning deterministically very close to nuclear speckles have higher numbers of total genes, the most highly expressed genes, housekeeping genes, genes with low transcriptional pausing, and super-enhancers. Our results demonstrate the capability of TSA-Seq for genome-wide mapping of nuclear structure and suggest a new model for spatial organization of transcription and gene expression.
24

Jowhar, Ziad, Sigal Shachar, Prabhakar R. Gudla, Darawalee Wangsa, Erin Torres, Jill L. Russ, Gianluca Pegoraro, Thomas Ried, Armin Raznahan, and Tom Misteli. "Effects of human sex chromosome dosage on spatial chromosome organization." Molecular Biology of the Cell 29, no. 20 (October 2018): 2458–69. http://dx.doi.org/10.1091/mbc.e18-06-0359.

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Sex chromosome aneuploidies (SCAs) are common genetic syndromes characterized by the presence of an aberrant number of X and Y chromosomes due to meiotic defects. These conditions impact the structure and function of diverse tissues, but the proximal effects of SCAs on genome organization are unknown. Here, to determine the consequences of SCAs on global genome organization, we have analyzed multiple architectural features of chromosome organization in a comprehensive set of primary cells from SCA patients with various ratios of X and Y chromosomes by use of imaging-based high-throughput chromosome territory mapping (HiCTMap). We find that X chromosome supernumeracy does not affect the size, volume, or nuclear position of the Y chromosome or an autosomal chromosome. In contrast, the active X chromosome undergoes architectural changes as a function of increasing X copy number as measured by a decrease in size and an increase in circularity, which is indicative of chromatin compaction. In Y chromosome supernumeracy, Y chromosome size is reduced suggesting higher chromatin condensation. The radial positioning of chromosomes is unaffected in SCA karyotypes. Taken together, these observations document changes in genome architecture in response to alterations in sex chromosome numbers and point to trans-effects of dosage compensation on chromosome organization.
25

Zhou, Tianming, Ruochi Zhang, and Jian Ma. "The 3D Genome Structure of Single Cells." Annual Review of Biomedical Data Science 4, no. 1 (July 20, 2021): 21–41. http://dx.doi.org/10.1146/annurev-biodatasci-020121-084709.

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The spatial organization of the genome in the cell nucleus is pivotal to cell function. However, how the 3D genome organization and its dynamics influence cellular phenotypes remains poorly understood. The very recent development of single-cell technologies for probing the 3D genome, especially single-cell Hi-C (scHi-C), has ushered in a new era of unveiling cell-to-cell variability of 3D genome features at an unprecedented resolution. Here, we review recent developments in computational approaches to the analysis of scHi-C, including data processing, dimensionality reduction, imputation for enhancing data quality, and the revealing of 3D genome features at single-cell resolution. While much progress has been made in computational method development to analyze single-cell 3D genomes, substantial future work is needed to improve data interpretation and multimodal data integration, which are critical to reveal fundamental connections between genome structure and function among heterogeneous cell populations in various biological contexts.
26

Federico, Concetta, Francesca Bruno, Denise Ragusa, Craig S. Clements, Desiree Brancato, Marianne P. Henry, Joanna M. Bridger, Sabrina Tosi, and Salvatore Saccone. "Chromosomal Rearrangements and Altered Nuclear Organization: Recent Mechanistic Models in Cancer." Cancers 13, no. 22 (November 22, 2021): 5860. http://dx.doi.org/10.3390/cancers13225860.

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The last decade has seen significant progress in understanding how the genome is organized spatially within interphase nuclei. Recent analyses have confirmed earlier molecular cytogenetic studies on chromosome positioning within interphase nuclei and provided new information about the topologically associated domains (TADs). Examining the nuances of how genomes are organized within interphase nuclei will provide information fundamental to understanding gene regulation and expression in health and disease. Indeed, the radial spatial positioning of individual gene loci within nuclei has been associated with up- and down-regulation of specific genes, and disruption of normal genome organization within nuclei will result in compromised cellular health. In cancer cells, where reorganization of the nuclear architecture may occur in the presence of chromosomal rearrangements such as translocations, inversions, or deletions, gene repositioning can change their expression. To date, very few studies have focused on radial gene positioning and the correlation to gene expression in cancers. Further investigations would improve our understanding of the biological mechanisms at the basis of cancer and, in particular, in leukemia initiation and progression, especially in those cases where the molecular consequences of chromosomal rearrangements are still unclear. In this review, we summarize the main milestones in the field of genome organization in the nucleus and the alterations to this organization that can lead to cancer diseases.
27

Szałaj, Przemysław, Zhonghui Tang, Paul Michalski, Michal J. Pietal, Oscar J. Luo, Michał Sadowski, Xingwang Li, Kamen Radew, Yijun Ruan, and Dariusz Plewczynski. "An integrated 3-Dimensional Genome Modeling Engine for data-driven simulation of spatial genome organization." Genome Research 26, no. 12 (October 27, 2016): 1697–709. http://dx.doi.org/10.1101/gr.205062.116.

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28

Lenz, Todd, and Karine G. Le Roch. "Three-Dimensional Genome Organization and Virulence in Apicomplexan Parasites." Epigenetics Insights 12 (January 2019): 251686571987943. http://dx.doi.org/10.1177/2516865719879436.

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Mounting evidence supports the idea that epigenetic, and the overall 3-dimensional (3D) architecture of the genome, plays an important role in gene expression for eukaryotic organisms. We recently used Hi-C methodologies to generate and compare the 3D genome of 7 different apicomplexan parasites, including several pathogenic and less pathogenic malaria parasites as well as related human parasites Babesia microti and Toxoplasma gondii. Our goal was to understand the possible relationship between genome organization, gene expression, and pathogenicity of these infectious agents. Collectively, our results demonstrate that spatial genome organization in most Plasmodium species is constrained by the colocalization of virulence genes that are unique in their effect on chromosome folding, indicating a link between genome organization and gene expression in more virulent pathogens.
29

Huang, Shao-Kuei, Peter H. Whitney, Sayantan Dutta, Stanislav Y. Shvartsman, and Christine A. Rushlow. "Spatial organization of transcribing loci during early genome activation in Drosophila." Current Biology 31, no. 22 (November 2021): 5102–10. http://dx.doi.org/10.1016/j.cub.2021.09.027.

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30

Chen, Changya, Wenbao Yu, Joanna Tober, Peng Gao, Bing He, Kiwon Lee, Tuan Trieu, Gerd A. Blobel, Nancy A. Speck, and Kai Tan. "Spatial Genome Re-organization between Fetal and Adult Hematopoietic Stem Cells." Cell Reports 29, no. 12 (December 2019): 4200–4211. http://dx.doi.org/10.1016/j.celrep.2019.11.065.

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31

Randise-Hinchliff, Carlo, and Jason H. Brickner. "Transcription factors dynamically control the spatial organization of the yeast genome." Nucleus 7, no. 4 (July 3, 2016): 369–74. http://dx.doi.org/10.1080/19491034.2016.1212797.

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32

Gavrilov, A. A., and S. V. Razin. "Compartmentalization of the cell nucleus and spatial organization of the genome." Molecular Biology 49, no. 1 (January 2015): 21–39. http://dx.doi.org/10.1134/s0026893315010033.

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33

Soutoglou, E., and T. Misteli. "On the Contribution of Spatial Genome Organization to Cancerous Chromosome Translocations." JNCI Monographs 2008, no. 39 (July 1, 2008): 16–19. http://dx.doi.org/10.1093/jncimonographs/lgn017.

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34

Stefanova, Maria E., Elizabeth Ing-Simmons, Stefan Stefanov, Ilya Flyamer, Heathcliff Dorado Garcia, Robert Schöpflin, Anton G. Henssen, Juan M. Vaquerizas, and Stefan Mundlos. "Doxorubicin Changes the Spatial Organization of the Genome around Active Promoters." Cells 12, no. 15 (August 4, 2023): 2001. http://dx.doi.org/10.3390/cells12152001.

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In this study, we delve into the impact of genotoxic anticancer drug treatment on the chromatin structure of human cells, with a particular focus on the effects of doxorubicin. Using Hi-C, ChIP-seq, and RNA-seq, we explore the changes in chromatin architecture brought about by doxorubicin and ICRF193. Our results indicate that physiologically relevant doses of doxorubicin lead to a local reduction in Hi-C interactions in certain genomic regions that contain active promoters, with changes in chromatin architecture occurring independently of Top2 inhibition, cell cycle arrest, and differential gene expression. Inside the regions with decreased interactions, we detected redistribution of RAD21 around the peaks of H3K27 acetylation. Our study also revealed a common structural pattern in the regions with altered architecture, characterized by two large domains separated from each other. Additionally, doxorubicin was found to increase CTCF binding in H3K27 acetylated regions. Furthermore, we discovered that Top2-dependent chemotherapy causes changes in the distance decay of Hi-C contacts, which are driven by direct and indirect inhibitors. Our proposed model suggests that doxorubicin-induced DSBs cause cohesin redistribution, which leads to increased insulation on actively transcribed TAD boundaries. Our findings underscore the significant impact of genotoxic anticancer treatment on the chromatin structure of the human genome.
35

Castellana, Michele, Sophia Hsin-Jung Li, and Ned S. Wingreen. "Spatial organization of bacterial transcription and translation." Proceedings of the National Academy of Sciences 113, no. 33 (August 2, 2016): 9286–91. http://dx.doi.org/10.1073/pnas.1604995113.

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In bacteria such as Escherichia coli, DNA is compacted into a nucleoid near the cell center, whereas ribosomes—molecular complexes that translate mRNAs into proteins—are mainly localized to the poles. We study the impact of this spatial organization using a minimal reaction–diffusion model for the cellular transcriptional–translational machinery. Although genome-wide mRNA-nucleoid segregation still lacks experimental validation, our model predicts that ∼90% of mRNAs are segregated to the poles. In addition, our analysis reveals a “circulation” of ribosomes driven by the flux of mRNAs, from synthesis in the nucleoid to degradation at the poles. We show that our results are robust with respect to multiple, biologically relevant factors, such as mRNA degradation by RNase enzymes, different phases of the cell division cycle and growth rates, and the existence of nonspecific, transient interactions between ribosomes and mRNAs. Finally, we confirm that the observed nucleoid size stems from a balance between the forces that the chromosome and mRNAs exert on each other. This suggests a potential global feedback circuit in which gene expression feeds back on itself via nucleoid compaction.
36

Liang, Jiangtao, Simon M. Bondarenko, Igor V. Sharakhov, and Maria V. Sharakhova. "Visualization of the Linear and Spatial Organization of Chromosomes in Mosquitoes." Cold Spring Harbor Protocols 2022, no. 12 (August 5, 2022): pdb.top107732. http://dx.doi.org/10.1101/pdb.top107732.

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Mosquitoes are vectors of dangerous human diseases such as malaria, dengue, Zika, West Nile fever, and lymphatic filariasis. Visualization of the linear and spatial organization of mosquito chromosomes is important for understanding genome structure and function. Utilization of chromosomal inversions as markers for population genetics studies yields insights into mosquito adaptation and evolution. Cytogenetic approaches assist with the development of chromosome-scale genome assemblies that are useful tools for studying mosquito biology and for designing novel vector control strategies. Fluorescence in situ hybridization is a powerful technique for localizing specific DNA sequences within the linear chromosome structure and within the spatial organization of the cell nucleus. Here, we introduce protocols used in our laboratories for chromosome visualization and their application in mosquitoes.
37

Kantidze, Omar L., and Sergey V. Razin. "Weak interactions in higher-order chromatin organization." Nucleic Acids Research 48, no. 9 (April 20, 2020): 4614–26. http://dx.doi.org/10.1093/nar/gkaa261.

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Abstract The detailed principles of the hierarchical folding of eukaryotic chromosomes have been revealed during the last two decades. Along with structures composing three-dimensional (3D) genome organization (chromatin compartments, topologically associating domains, chromatin loops, etc.), the molecular mechanisms that are involved in their establishment and maintenance have been characterized. Generally, protein–protein and protein–DNA interactions underlie the spatial genome organization in eukaryotes. However, it is becoming increasingly evident that weak interactions, which exist in biological systems, also contribute to the 3D genome. Here, we provide a snapshot of our current understanding of the role of the weak interactions in the establishment and maintenance of the 3D genome organization. We discuss how weak biological forces, such as entropic forces operating in crowded solutions, electrostatic interactions of the biomolecules, liquid-liquid phase separation, DNA supercoiling, and RNA environment participate in chromosome segregation into structural and functional units and drive intranuclear functional compartmentalization.
38

Di Pierro, Michele, Davit A. Potoyan, Peter G. Wolynes, and José N. Onuchic. "Anomalous diffusion, spatial coherence, and viscoelasticity from the energy landscape of human chromosomes." Proceedings of the National Academy of Sciences 115, no. 30 (July 9, 2018): 7753–58. http://dx.doi.org/10.1073/pnas.1806297115.

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The nucleus of a eukaryotic cell is a nonequilibrium system where chromatin is subjected to active processes that continuously rearrange it over the cell’s life cycle. Tracking the motion of chromosomal loci provides information about the organization of the genome and the physical processes shaping that organization. Optical experiments report that loci move with subdiffusive dynamics and that there is spatially coherent motion of the chromatin. We recently showed that it is possible to predict the 3D architecture of genomes through a physical model for chromosomes that accounts for the biochemical interactions mediated by proteins and regulated by epigenetic markers through a transferable energy landscape. Here, we study the temporal dynamics generated by this quasi-equilibrium energy landscape assuming Langevin dynamics at an effective temperature. Using molecular dynamics simulations of two interacting human chromosomes, we show that the very same interactions that account for genome architecture naturally reproduce the spatial coherence, viscoelasticity, and the subdiffusive behavior of the motion in interphase chromosomes as observed in numerous experiments. The agreement between theory and experiments suggests that even if active processes are involved, an effective quasi-equilibrium landscape model can largely mimic their dynamical effects.
39

Williams, Adam, and Richard A. Flavell. "The role of CTCF in regulating nuclear organization." Journal of Experimental Medicine 205, no. 4 (March 17, 2008): 747–50. http://dx.doi.org/10.1084/jem.20080066.

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The spatial organization of the genome is thought to play an important part in the coordination of gene regulation. New techniques have been used to identify specific long-range interactions between distal DNA sequences, revealing an ever-increasing complexity to nuclear organization. CCCTC-binding factor (CTCF) is a versatile zinc finger protein with diverse regulatory functions. New data now help define how CTCF mediates both long-range intrachromosomal and interchromosomal interactions, and highlight CTCF as an important factor in determining the three-dimensional structure of the genome.
40

Kim, Yoori, and Hongtao Yu. "Shaping of the 3D genome by the ATPase machine cohesin." Experimental & Molecular Medicine 52, no. 12 (December 2020): 1891–97. http://dx.doi.org/10.1038/s12276-020-00526-2.

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AbstractThe spatial organization of the genome is critical for fundamental biological processes, including transcription, genome replication, and segregation. Chromatin is compacted and organized with defined patterns and proper dynamics during the cell cycle. Aided by direct visualization and indirect genome reconstruction tools, recent discoveries have advanced our understanding of how interphase chromatin is dynamically folded at the molecular level. Here, we review the current understanding of interphase genome organization with a focus on the major regulator of genome structure, the cohesin complex. We further discuss how cohesin harnesses the energy of ATP hydrolysis to shape the genome by extruding chromatin loops.
41

Wang, Qixuan, Juan Wang, Radhika Mathur, Mark W. Youngblood, Qiushi Jin, Ye Hou, Lena A. Stasiak, Yu Luan, Joseph F. Costello, and Feng Yue. "Abstract 5676: Spatial 3D genome organization reveals intratumor heterogeneity in primary glioblastoma samples." Cancer Research 84, no. 6_Supplement (March 22, 2024): 5676. http://dx.doi.org/10.1158/1538-7445.am2024-5676.

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Abstract Glioblastoma (GBM) represents the most prevalent malignant primary brain tumor with highly unfavorable prognosis. Currently, most genomic studies are conducted at a single site of a tumor, which do not reflect the complete genetic or epigenetic information across the whole tumor. Furthermore, the intra-tumoral heterogeneity (ITH) of 3D genome organization has also not been studied yet. To address these gaps, we performed Hi-C experiments in 21 samples obtained from 9 GBM patients, with 15 of them being spatially mapped based on their 3D coordinates from the same patients. We identified extensive inter-tumoral and intra-tumoral heterogeneity in genome compartmentalization and chromatin interactions. Notably, in a patient with 9 spatially mapped samples from both temporal and frontal regions, we accumulated over 6 billion reads and defined high-resolution region-specific chromatin interactions, regulatory networks, and key regulators within the same patient. We detected structural variation (SV) and enhancer hijacking across all the samples, and identified recurrent events that affect known cancer-related genes such as CDKN2A/B. Finally, we introduce the concept of 'enhancer amputation', defined as the loss of enhancers due to SVs which lead to decreased expression of their original target genes. To our knowledge, this study represents the first large-scale exploration of the 3D genome in primary GBM patients and the first investigation of 3D genome organization in multiple regions of the same tumor. Our findings provide unprecedented insights into the ITH of GBM at the 3D genomic level, opening new avenues for understanding and potentially targeting this devastating disease. Citation Format: Qixuan Wang, Juan Wang, Radhika Mathur, Mark W. Youngblood, Qiushi Jin, Ye Hou, Lena A. Stasiak, Yu Luan, Joseph F. Costello, Feng Yue. Spatial 3D genome organization reveals intratumor heterogeneity in primary glioblastoma samples [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5676.
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Bunnik, Evelien M., Aarthi Venkat, Jianlin Shao, Kathryn E. McGovern, Gayani Batugedara, Danielle Worth, Jacques Prudhomme, et al. "Comparative 3D genome organization in apicomplexan parasites." Proceedings of the National Academy of Sciences 116, no. 8 (February 5, 2019): 3183–92. http://dx.doi.org/10.1073/pnas.1810815116.

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The positioning of chromosomes in the nucleus of a eukaryotic cell is highly organized and has a complex and dynamic relationship with gene expression. In the human malaria parasite Plasmodium falciparum, the clustering of a family of virulence genes correlates with their coordinated silencing and has a strong influence on the overall organization of the genome. To identify conserved and species-specific principles of genome organization, we performed Hi-C experiments and generated 3D genome models for five Plasmodium species and two related apicomplexan parasites. Plasmodium species mainly showed clustering of centromeres, telomeres, and virulence genes. In P. falciparum, the heterochromatic virulence gene cluster had a strong repressive effect on the surrounding nuclear space, while this was less pronounced in Plasmodium vivax and Plasmodium berghei, and absent in Plasmodium yoelii. In Plasmodium knowlesi, telomeres and virulence genes were more dispersed throughout the nucleus, but its 3D genome showed a strong correlation with gene expression. The Babesia microti genome showed a classical Rabl organization with colocalization of subtelomeric virulence genes, while the Toxoplasma gondii genome was dominated by clustering of the centromeres and lacked virulence gene clustering. Collectively, our results demonstrate that spatial genome organization in most Plasmodium species is constrained by the colocalization of virulence genes. P. falciparum and P. knowlesi, the only two Plasmodium species with gene families involved in antigenic variation, are unique in the effect of these genes on chromosome folding, indicating a potential link between genome organization and gene expression in more virulent pathogens.
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Jacobson, E., M. H. Vickers, J. K. Perry, and J. M. O’Sullivan. "Genome organization: connecting the developmental origins of disease and genetic variation." Journal of Developmental Origins of Health and Disease 9, no. 3 (August 29, 2017): 260–65. http://dx.doi.org/10.1017/s2040174417000678.

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An adverse early life environment can increase the risk of metabolic and other disorders later in life. Genetic variation can modify an individual’s susceptibility to these environmental challenges. These gene by environment interactions are important, but difficult, to dissect. The nucleus is the primary organelle where environmental responses impact directly on the genetic variants within the genome, resulting in changes to the biology of the genome and ultimately the phenotype. Understanding genome biology requires the integration of the linear DNA sequence, epigenetic modifications and nuclear proteins that are present within the nucleus. The interactions between these layers of information may be captured in the emergent spatial genome organization. As such genome organization represents a key research area for decoding the role of genetic variation in the Developmental Origins of Health and Disease.
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Razin, S. V. "Spatial organization of the eukaryotic genome and the action of epigenetic mechanisms." Russian Journal of Genetics 42, no. 12 (December 2006): 1353–61. http://dx.doi.org/10.1134/s1022795406120015.

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Plaza-Jennings, Amara, Aditi Valada, and Schahram Akbarian. "3D Genome Plasticity in Normal and Diseased Neurodevelopment." Genes 13, no. 11 (November 1, 2022): 1999. http://dx.doi.org/10.3390/genes13111999.

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Non-random spatial organization of the chromosomal material inside the nuclei of brain cells emerges as an important regulatory layer of genome organization and function in health and disease. Here, we discuss how integrative approaches assessing chromatin in context of the 3D genome is providing new insights into normal and diseased neurodevelopment. Studies in primate (incl. human) and rodent brain have confirmed that chromosomal organization in neurons and glia undergoes highly dynamic changes during pre- and early postnatal development, with potential for plasticity across a much wider age window. For example, neuronal 3D genomes from juvenile and adult cerebral cortex and hippocampus undergo chromosomal conformation changes at hundreds of loci in the context of learning and environmental enrichment, viral infection, and neuroinflammation. Furthermore, locus-specific structural DNA variations, such as micro-deletions, duplications, repeat expansions, and retroelement insertions carry the potential to disrupt the broader epigenomic and transcriptional landscape far beyond the boundaries of the site-specific variation, highlighting the critical importance of long-range intra- and inter-chromosomal contacts for neuronal and glial function.
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Erenpreisa, Jekaterina, Alessandro Giuliani, Kenichi Yoshikawa, Martin Falk, Georg Hildenbrand, Kristine Salmina, Talivaldis Freivalds, et al. "Spatial-Temporal Genome Regulation in Stress-Response and Cell-Fate Change." International Journal of Molecular Sciences 24, no. 3 (January 31, 2023): 2658. http://dx.doi.org/10.3390/ijms24032658.

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Complex functioning of the genome in the cell nucleus is controlled at different levels: (a) the DNA base sequence containing all relevant inherited information; (b) epigenetic pathways consisting of protein interactions and feedback loops; (c) the genome architecture and organization activating or suppressing genetic interactions between different parts of the genome. Most research so far has shed light on the puzzle pieces at these levels. This article, however, attempts an integrative approach to genome expression regulation incorporating these different layers. Under environmental stress or during cell development, differentiation towards specialized cell types, or to dysfunctional tumor, the cell nucleus seems to react as a whole through coordinated changes at all levels of control. This implies the need for a framework in which biological, chemical, and physical manifestations can serve as a basis for a coherent theory of gene self-organization. An international symposium held at the Biomedical Research and Study Center in Riga, Latvia, on 25 July 2022 addressed novel aspects of the abovementioned topic. The present article reviews the most recent results and conclusions of the state-of-the-art research in this multidisciplinary field of science, which were delivered and discussed by scholars at the Riga symposium.
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Neems, Daniel S., Arturo G. Garza-Gongora, Erica D. Smith, and Steven T. Kosak. "Topologically associated domains enriched for lineage-specific genes reveal expression-dependent nuclear topologies during myogenesis." Proceedings of the National Academy of Sciences 113, no. 12 (March 8, 2016): E1691—E1700. http://dx.doi.org/10.1073/pnas.1521826113.

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The linear distribution of genes across chromosomes and the spatial localization of genes within the nucleus are related to their transcriptional regulation. The mechanistic consequences of linear gene order, and how it may relate to the functional output of genome organization, remain to be fully resolved, however. Here we tested the relationship between linear and 3D organization of gene regulation during myogenesis. Our analysis has identified a subset of topologically associated domains (TADs) that are significantly enriched for muscle-specific genes. These lineage-enriched TADs demonstrate an expression-dependent pattern of nuclear organization that influences the positioning of adjacent nonenriched TADs. Therefore, lineage-enriched TADs inform cell-specific genome organization during myogenesis. The reduction of allelic spatial distance of one of these domains, which contains Myogenin, correlates with reduced transcriptional variability, identifying a potential role for lineage-specific nuclear topology. Using a fusion-based strategy to decouple mitosis and myotube formation, we demonstrate that the cell-specific topology of syncytial nuclei is dependent on cell division. We propose that the effects of linear and spatial organization of gene loci on gene regulation are linked through TAD architecture, and that mitosis is critical for establishing nuclear topologies during cellular differentiation.
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Powell, D., D. G. Cran, C. Jennings, and R. Jones. "Spatial organization of repetitive DNA sequences in the bovine sperm nucleus." Journal of Cell Science 97, no. 1 (September 1, 1990): 185–91. http://dx.doi.org/10.1242/jcs.97.1.185.

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During spermatogenesis, DNA in the sperm head becomes more tightly condensed as histones are replaced by protamine-like molecules. In this article, the question is asked whether, during the production of this highly differentiated cell, controls are imposed on the spatial organization of DNA within the nucleus. Heads from bull spermatozoa were isolated by a technique that removed the plasma membrane and acrosomal contents, and the DNA was induced to decondense by addition of 2-mercaptoethanol and trypsin. Under these conditions, decondensation was induced in all regions of the head. To determine whether there was any spatial restraint on packaging of the genome, three DNA probes were used (pl.709-512, containing an interspersed repetitive sequence; pCSIH, containing a copy of the major bovine centromeric statellite sequence; p18 s and p28 s, containing the 18 S and 28 S ribosomal genes) that might be expected to hybridize to different regions. Results showed that the interspersed repetitive probe hybridized to all regions of the head, whereas the ribosomal and centromeric probes hybridized to sequences that were largely confined to the equatorial region of the sperm. We conclude that organization of the genome in the bovine sperm nucleus is not random.
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Wu, Shuai, Nail Fatkhutdinov, Leah Rosin, Jennifer M. Luppino, Osamu Iwasaki, Hideki Tanizawa, Hsin-Yao Tang, et al. "ARID1A spatially partitions interphase chromosomes." Science Advances 5, no. 5 (May 2019): eaaw5294. http://dx.doi.org/10.1126/sciadv.aaw5294.

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ARID1A, a subunit of the SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin-remodeling complex, localizes to both promoters and enhancers to influence transcription. However, the role of ARID1A in higher-order spatial chromosome partitioning and genome organization is unknown. Here, we show that ARID1A spatially partitions interphase chromosomes and regulates higher-order genome organization. The SWI/SNF complex interacts with condensin II, and they display significant colocalizations at enhancers. ARID1A knockout drives the redistribution of condensin II preferentially at enhancers, which positively correlates with changes in transcription. ARID1A and condensin II contribute to transcriptionally inactive B-compartment formation, while ARID1A weakens the border strength of topologically associated domains. Condensin II redistribution induced by ARID1A knockout positively correlates with chromosome sizes, which negatively correlates with interchromosomal interactions. ARID1A loss increases the trans interactions of small chromosomes, which was validated by three-dimensional interphase chromosome painting. These results demonstrate that ARID1A is important for large-scale genome folding and spatially partitions interphase chromosomes.
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Dias, João Diogo, Nazim Sarica, Axel Cournac, Romain Koszul, and Christine Neuveut. "Crosstalk between Hepatitis B Virus and the 3D Genome Structure." Viruses 14, no. 2 (February 21, 2022): 445. http://dx.doi.org/10.3390/v14020445.

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Viruses that transcribe their DNA within the nucleus have to adapt to the existing cellular mechanisms that govern transcriptional regulation. Recent technological breakthroughs have highlighted the highly hierarchical organization of the cellular genome and its role in the regulation of gene expression. This review provides an updated overview on the current knowledge on how the hepatitis B virus interacts with the cellular 3D genome and its consequences on viral and cellular gene expression. We also briefly discuss the strategies developed by other DNA viruses to co-opt and sometimes subvert cellular genome spatial organization.

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