Cohesin-mediated interactions organize chromosomal domain architecture

Sevil Sofueva, Eitan Yaffe, Wen-Ching Chan, Dimitra Georgopoulou, Matteo Vietri Rudan, Hegias Mira-Bontenbal, Steven M Pollard, Gary P Schroth, Amos Tanay, Suzana Hadjur

Research output: Contribution to journalArticlepeer-review

Abstract

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.
Original languageEnglish
Pages (from-to)3119-29
Number of pages11
JournalEMBO Journal
Volume32
Issue number24
DOIs
Publication statusPublished - 1 Nov 2013

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