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Cohesin-mediated interactions organize chromosomal domain architecture.

TitleCohesin-mediated interactions organize chromosomal domain architecture.
Publication TypeJournal Article
Year of Publication2013
AuthorsSofueva S, Yaffe E, Chan W-C, Georgopoulou D, Rudan MVietri, Mira-Bontenbal H, Pollard SM, Schroth GP, Tanay A, Hadjur S
JournalEMBO J
Date Published2013 Dec 11
KeywordsAnimals, Catalytic Domain, Cell Cycle Proteins, Cell Proliferation, Cells, Cultured, Chromosomal Proteins, Non-Histone, Chromosomes, Gene Expression Regulation, Mice, Mitosis, Nuclear Proteins, Phosphoproteins, Repressor Proteins, Stem Cells, Transcription, Genetic

To ensure proper gene regulation within constrained nuclear space, chromosomes facilitate access to transcribed regions, while compactly packaging all other information. Recent studies revealed that chromosomes are organized into megabase-scale domains that demarcate active and inactive genetic elements, suggesting that compartmentalization is important for genome function. Here, we show that very specific long-range interactions are anchored by cohesin/CTCF sites, but not cohesin-only or CTCF-only sites, to form a hierarchy of chromosomal loops. These loops demarcate topological domains and form intricate internal structures within them. Post-mitotic nuclei deficient for functional cohesin exhibit global architectural changes associated with loss of cohesin/CTCF contacts and relaxation of topological domains. Transcriptional analysis shows that this cohesin-dependent perturbation of domain organization leads to widespread gene deregulation of both cohesin-bound and non-bound genes. Our data thereby support a role for cohesin in the global organization of domain structure and suggest that domains function to stabilize the transcriptional programmes within them.

Alternate JournalEMBO J.
PubMed ID24185899
Grant ListG0900491 / / Medical Research Council / United Kingdom
G0900491/1 / / Medical Research Council / United Kingdom
G1001649 / / Medical Research Council / United Kingdom
G1001649 / / Medical Research Council / United Kingdom
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