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Conserved Topological Domains in Mammalian Genomes Identified by High-resolution Analysis of Chromatin Interactions

ABSTRACT: The spatial organization of the genome is intimately linked to its biological function, yet our understanding of higher order genomic structure is limited. Here we present high-resolution analyses of chromosomal organization in pluripotent and differentiated human and murine cell types determined using the Hi-C technique. We find that the mammalian genome is composed of over 1000 topological domains, which are stable among different cell types and highly conserved across species. These megabase-long genomic structures, defined by prominent local chromatin interactions and separated by narrow boundary regions, likely function to restrict regulatory interactions between cis-acting elements and limit the spreading of heterochromatin during cellular differentiation. Interestingly, the boundaries are enriched not only for binding sites of the insulator protein CTCF, but also for promoters of house keeping genes, supporting a role for both CTCF and housekeeping genes in the establishment or maintenance of the topological domains.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE35156 | GEO | 2012/04/10

SECONDARY ACCESSION(S): PRJNA150781

REPOSITORIES: GEO

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Conserved Topological Domains in Mammalian Genomes Identified by High-resolution Analysis of Chromatin Interactions

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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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