A Compendium of Chromatin Contact Maps Reveal Spatially Active Regions in the Human Genome
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ABSTRACT:
ORGANISM(S): Mus musculus Homo sapiens
PROVIDER: GSE87112 | GEO | 2016/11/15
SECONDARY ACCESSION(S): PRJNA343608
REPOSITORIES: GEO
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Project description:Eukaryotic genomes are folded into three-dimensional structures that govern diverse hromosomal procsses. Studeis in Drosophila and mammals have revealed large self-associating tomological domains whose borders are enriched in cohesin/CTCF factors that are required for long-range intrations. However, mechanisms governing higher-order folding of chromatin fivbers and the exact function of cohesin in this process remain poor understood. Here we perform Hi-C to explore the organization of the Schizosaccharomyces pombe genome at high-resolution, which despite its small size comprises fundamental features found in higher eukaryotes. Our analyses reveal that in addition to determinants of Rabl-like chromosome architecture, smaller locally interacting regions of chromatin, referred to as globules, are a distinctive features of S. pombe chromosome organization. This feature of chromatin architecture requires a function of cohesin distinct from its role in sister chromatid cohesion. Cohesin is enriched at globule boundaries and its loss causes disruption of local globule structure and global chromosome territories. Heterochromatin, which selectively loads cohesin at specific loci including pericentromric and subtelomeric domains, is dispensable for globule formation but uniquely impacts genome organization through chromatin compaction by enforcing Rabl configuration. microarray CGH analysis in mutant fission yeast cell; Copy number change in rad21-K1 were examined by comparative genomic hybridization analysis.
2014-10-22 | E-GEOD-56847 | biostudies-arrayexpress
Project description:Eukaryotic genomes are folded into three-dimensional structures that govern diverse hromosomal procsses. Studeis in Drosophila and mammals have revealed large self-associating tomological domains whose borders are enriched in cohesin/CTCF factors that are required for long-range intrations. However, mechanisms governing higher-order folding of chromatin fivbers and the exact function of cohesin in this process remain poor understood. Here we perform Hi-C to explore the organization of the Schizosaccharomyces pombe genome at high-resolution, which despite its small size comprises fundamental features found in higher eukaryotes. Our analyses reveal that in addition to determinants of Rabl-like chromosome architecture, smaller locally interacting regions of chromatin, referred to as globules, are a distinctive features of S. pombe chromosome organization. This feature of chromatin architecture requires a function of cohesin distinct from its role in sister chromatid cohesion. Cohesin is enriched at globule boundaries and its loss causes disruption of local globule structure and global chromosome territories. Heterochromatin, which selectively loads cohesin at specific loci including pericentromric and subtelomeric domains, is dispensable for globule formation but uniquely impacts genome organization through chromatin compaction by enforcing Rabl configuration. Agilent 60mer oligonucleotide custom array containing probes spanning large portion of chromosome 2 at 50bp resolution was used to profile expression levels in mutant cells and to compare them to levels in wild type cells.
2014-10-22 | E-GEOD-57159 | biostudies-arrayexpress
Project description:ChIP-chip analyses of Psc3 in wild-type and mutant fission yeast cells. Eukaryotic genomes are folded into three-dimensional structures that govern diverse hromosomal procsses. Studeis in Drosophila and mammals have revealed large self-associating tomological domains whose borders are enriched in cohesin/CTCF factors that are required for long-range intrations. However, mechanisms governing higher-order folding of chromatin fivbers and the exact function of cohesin in this process remain poor understood. Here we perform Hi-C to explore the organization of the Schizosaccharomyces pombe genome at high-resolution, which despite its small size comprises fundamental features found in higher eukaryotes. Our analyses reveal that in addition to determinants of Rabl-like chromosome architecture, smaller locally interacting regions of chromatin, referred to as globules, are a distinctive features of S. pombe chromosome organization. This feature of chromatin architecture requires a function of cohesin distinct from its role in sister chromatid cohesion. Cohesin is enriched at globule boundaries and its loss causes disruption of local globule structure and global chromosome territories. Heterochromatin, which selectively loads cohesin at specific loci including pericentromric and subtelomeric domains, is dispensable for globule formation but uniquely impacts genome organization through chromatin compaction by enforcing Rabl configuration. Genome-wide distribution of Psc3 were determined by ChIP-chip analysis in wild-type and mutant fission yeast cells.
2014-10-22 | E-GEOD-56848 | biostudies-arrayexpress
Project description:Recent studies of genome-wide chromatin interactions have revealed that the human genome is partitioned into many self-associating topological domains. The boundary sequences are enriched for binding sites of CTCF and the cohesin complex, implicating these two factors in the establishment or maintenance of topological domains. To determine the role of cohesin and CTCF in higher order chromatin architecture in human cells, we proteolytically cleaved the cohesin complex from interphase chromatin and examined changes in chromosomal organization as well as transcriptome. We observed a general loss of local chromosomal interactions upon disruption of cohesin complex, but the topological domains remain intact. However, we found that depletion of CTCF by RNA interference in these cells not only reduced intra-domain interactions but also increased inter-domain interactions. Further more, distinct groups of genes become mis-regulated upon depletion of cohesin and CTCF. Taken together, these observations suggest that CTCF and cohesin contribute in different ways to chromatin organization and gene regulation. Hi-C and mRNA-seq experiments in Cohesin and CTCF depleted HEK293 cells
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Project description:We employed in situ Hi-C with an auxin-inducible degron (AID) system to demonstrate the effect of chromatin remodeling on 3D genome organization in yeast.
2021-09-29 | GSE158336 | GEO
Project description:Eukaryotic genomes are folded into a hierarchy of three-dimensional structures that impact nuclear functions, including transcription, replication, and repair1-3. Studies in Drosophila and mammals have revealed megabase-sized topologically associated domains (TADs) within chromosomes, which in turn are spatially restricted within the nucleus4-8. However, little is known about local physical constraints that drive higher-order folding of chromosomes. Here we performed Hi-C analysis of the fission yeast Schizosaccharomyces pombe to explore genome organization at high resolution. S. pombe comprises a small genome ideal for examining structural features of chromatin folding, and contains fundamental components present in higher eukaryotes. Large domains of heterochromatin coat centromeres and telomeres and recruit cohesin, a ring-like protein complex that binds sister chromatids and mediates long range looping of interphase chromosomes. Our analyses reveal a highly ordered chromosome organization, consistent with a Rabl configuration, which is dependent on constraints imposed at centromeres and telomeres. We find that local chromatin compaction and cohesin recruitment to centromeres mediated by heterochromatin is required for maintaining global genome territorial restraint. In addition to larger complex domains, we also observed locally interacting regions of chromatin ~50 kilobases long, which organize chromosome arms into structures referred to as “globules”. Globule boundaries are enriched in cohesin and convergent gene orientation. The role of cohesin in maintaining globule domains is independent of its role in sister chromatid cohesion, as globule domains are also a feature of G1 chromosome architecture. Defect in cohesin disrupts globule domains and results in an altered chromosome organization at larger scales, including the loss of chromosome territories. Disruption of globules also affects functional annotation of the genome, leading to impairment of borders between neighboring transcriptional units. Our analyses reveal key features of chromatin organization and folding and show that distinct mechanisms uniquely impact the hierarchy of genome organization to protect genome integrity and to coordinate nuclear functions. Comparison of HiC contact maps under various conditions reveal fundamental principles of genome organization
2014-10-22 | E-GEOD-57316 | biostudies-arrayexpress
Project description:The identification of cell-type-specific 3D chromatin interactions between regulatory elements can help to decipher gene regulation and to interpret the function of disease-associated non-coding variants. However, current chromosome conformation capture (3C) technologies are unable to resolve interactions at this resolution when only small numbers of cells are available as input. We therefore present ChromaFold, a deep learning model that predicts 3D contact maps and regulatory interactions from single-cell ATAC sequencing (scATAC-seq) data alone. ChromaFold uses pseudobulk chromatin accessibility, co-accessibility profiles across metacells, and predicted CTCF motif tracks as input features and employs a lightweight architecture to enable training on standard GPUs. Once trained on paired scATAC-seq and Hi-C data in human cell lines and tissues, ChromaFold can accurately predict both the 3D contact map and peak-level interactions across diverse human and mouse test cell types. In benchmarking against a recent deep learning method that uses bulk ATAC-seq, DNA sequence, and CTCF ChIP-seq to make cell-type-specific predictions, ChromaFold yields superior prediction performance when including CTCF ChIP-seq data as an input and comparable performance without. Finally, fine-tuning ChromaFold on paired scATAC-seq and Hi-C in a complex tissue enables deconvolution of chromatin interactions across cell subpopulations. ChromaFold thus achieves state-of-the-art prediction of 3D contact maps and regulatory interactions using scATAC-seq alone as input data, enabling accurate inference of celltype- specific interactions in settings where 3C-based assays are infeasible.
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Project description:Background: Structural maintenance of chromosomes (SMC) complexes are central organizers of chromatin architecture throughout the cell cycle. The SMC family member condensin is best known for establishing long-range chromatin interactions in mitosis. These compact chromatin and create mechanically stable chromosomes. How condensin contributes to chromatin organization in interphase is less well understood. Results: Here, we use efficient conditional depletion of fission yeast condensin to determine its contribution to interphase chromatin organization. We deplete condensin in G2 arrested cells to preempt confounding effects from cell cycle progression without condensin. Genome-wide chromatin interaction mapping, using Hi-C, reveals condensin-mediated chromatin interactions in interphase that are qualitatively similar to those observed in mitosis, but quantitatively far less prevalent. Despite its low abundance, chromatin mobility tracking shows that condensin markedly confines interphase chromatin movements. Without condensin, chromatin behaves as an unconstrained Rouse polymer with excluded volume, while condensin constrains its mobility. Unexpectedly, we find that condensin is required during interphase to prevent ongoing transcription from eliciting a DNA damage response. Conclusions: In addition to establishing mitotic chromosome architecture, condensin-mediated long-range chromatin interactions contribute to shaping chromatin organization in interphase. The resulting structure confines chromatin mobility and protects the genome from transcription-induced DNA damage. This adds to the important roles of condensin in maintaining chromosome stability.
2020-09-14 | GSE143338 | GEO
Project description:Eukaryotic genomes are folded into three-dimensional structures that govern diverse hromosomal procsses. Studeis in Drosophila and mammals have revealed large self-associating tomological domains whose borders are enriched in cohesin/CTCF factors that are required for long-range intrations. However, mechanisms governing higher-order folding of chromatin fivbers and the exact function of cohesin in this process remain poor understood. Here we perform Hi-C to explore the organization of the Schizosaccharomyces pombe genome at high-resolution, which despite its small size comprises fundamental features found in higher eukaryotes. Our analyses reveal that in addition to determinants of Rabl-like chromosome architecture, smaller locally interacting regions of chromatin, referred to as globules, are a distinctive features of S. pombe chromosome organization. This feature of chromatin architecture requires a function of cohesin distinct from its role in sister chromatid cohesion. Cohesin is enriched at globule boundaries and its loss causes disruption of local globule structure and global chromosome territories. Heterochromatin, which selectively loads cohesin at specific loci including pericentromric and subtelomeric domains, is dispensable for globule formation but uniquely impacts genome organization through chromatin compaction by enforcing Rabl configuration.
2014-10-22 | GSE57159 | GEO
Project description:Eukaryotic genomes are folded into three-dimensional structures that govern diverse hromosomal procsses. Studeis in Drosophila and mammals have revealed large self-associating tomological domains whose borders are enriched in cohesin/CTCF factors that are required for long-range intrations. However, mechanisms governing higher-order folding of chromatin fivbers and the exact function of cohesin in this process remain poor understood. Here we perform Hi-C to explore the organization of the Schizosaccharomyces pombe genome at high-resolution, which despite its small size comprises fundamental features found in higher eukaryotes. Our analyses reveal that in addition to determinants of Rabl-like chromosome architecture, smaller locally interacting regions of chromatin, referred to as globules, are a distinctive features of S. pombe chromosome organization. This feature of chromatin architecture requires a function of cohesin distinct from its role in sister chromatid cohesion. Cohesin is enriched at globule boundaries and its loss causes disruption of local globule structure and global chromosome territories. Heterochromatin, which selectively loads cohesin at specific loci including pericentromric and subtelomeric domains, is dispensable for globule formation but uniquely impacts genome organization through chromatin compaction by enforcing Rabl configuration.
2014-10-22 | GSE56847 | GEO