Journal article
Cohesin-mediated interactions organize chromosomal domain architecture
EMBO Journal, Vol.32(24), pp.3119-3129
Dec/2013
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.
Details
- Title
- Cohesin-mediated interactions organize chromosomal domain architecture
- Creators
- Sevil Sofueva (null)Eitan Yaffe (null) - 972WIS_INST___83Wen-Ching Chan (null)Dimitra Georgopoulou (null)Matteo Vietri Rudan (null)Hegias Mira-Bontenbal (null)Steven M. Pollard (null)Gary P. Schroth (null)Amos Tanay (null) - 972WIS_INST___83Suzana Hadjur (null)
- Resource Type
- Journal article
- Publication Details
- EMBO Journal, Vol.32(24), pp.3119-3129; Dec/2013
- Number of pages
- 11
- Language
- English
- DOI
- https://doi.org/10.1038/emboj.2013.237
- Grant note
- Medical Research Council [G0900491/1, G1001649]; EPIGENESYS EU NoE; ISF [1796/12]We wish to thank Zoe Webster for ESC preps; Andrew Oldfield for cell-culture support; Lu Zhang, Shujun Luo and Robin Li for help with library preparations and sequencing; Sreenivasulu Kurukuti and David Vetrie (Glasgow University) for help with Hi-C; Tomas Adejumo for cell sorting; Lauren McLaughlin and Anne Vaahtokari for help with microscopy; Ben Martynoga and Francois Guillemot for providing p300 ChIP data in NSCs; Gilad Landan for 4C-Seq advice; and Ephraim Kenigsberg for advice on analysis and data manipulation. We would also like to acknowledge members of the Hadjur and Tanay groups for discussions. This work was supported by the Medical Research Council (G0900491/1 and G1001649) granted to SH, the EPIGENESYS EU NoE (for SH and AT) and the ISF (grant number 1796/12 for AT). AT is an incumbent of the Rich Family CDC._ALMAME_DELIMITER_
- Record Identifier
- 993264898203596
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