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Cohesin‐mediated interactions organize chromosomal domain architecture
Author(s) -
Sofueva Sevil,
Yaffe Eitan,
Chan WenChing,
Georgopoulou Dimitra,
Vietri Rudan Matteo,
MiraBontenbal Hegias,
Pollard Steven M,
Schroth Gary P,
Tanay Amos,
Hadjur Suzana
Publication year - 2013
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2013.237
Subject(s) - cohesin , ctcf , biology , genetics , chromatin , chromosome segregation , genomic organization , computational biology , microbiology and biotechnology , gene , genome , chromosome , enhancer , gene expression
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.