Title | Cohesin-mediated interactions organize chromosomal domain architecture. |
Publication Type | Journal Article |
Year of Publication | 2013 |
Authors | Sofueva S, Yaffe E, Chan W-C, Georgopoulou D, Rudan MVietri, Mira-Bontenbal H, Pollard SM, Schroth GP, Tanay A, Hadjur S |
Journal | EMBO J |
Volume | 32 |
Issue | 24 |
Pagination | 3119-29 |
Date Published | 2013 Dec 11 |
ISSN | 1460-2075 |
Keywords | Animals, 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 |
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. |
DOI | 10.1038/emboj.2013.237 |
Alternate Journal | EMBO J. |
PubMed ID | 24185899 |
Grant List | G0900491 / / Medical Research Council / United Kingdom G0900491/1 / / Medical Research Council / United Kingdom G1001649 / / Medical Research Council / United Kingdom G1001649 / / Medical Research Council / United Kingdom |