Cohesin Loss Eliminates All Loop Domains
Name
nihms909480.pdf
Size
3.71 MB
Format
Adobe PDF
Checksum (MD5)
881dc8500a06a723a9aeac91d6bb3e7a
Author(s)
Rao, Suhas S.P.
Huang, Su-Chen
Glenn St Hilaire, Brian
Engreitz, Jesse M.
Perez, Elizabeth M.
Kieffer-Kwon, Kyong-Rim
Sanborn, Adrian L.
Johnstone, Sarah E.
Bascom, Gavin D.
Bochkov, Ivan D.
Date Issued
October 2017
Journal
Cell
Publisher
Elsevier
Citation
Rao, Suhas S.P. et al. “Cohesin Loss Eliminates All Loop Domains.” Cell 171, 2 (October 2017): 305–320 © 2017 Elsevier Inc
Version
Author's final manuscript
Abstract
The human genome folds to create thousands of intervals, called “contact domains,” that exhibit enhanced contact frequency within themselves. “Loop domains” form because of tethering between two loci—almost always bound by CTCF and cohesin—lying on the same chromosome. “Compartment domains” form when genomic intervals with similar histone marks co-segregate. Here, we explore the effects of degrading cohesin. All loop domains are eliminated, but neither compartment domains nor histone marks are affected. Loss of loop domains does not lead to widespread ectopic gene activation but does affect a significant minority of active genes. In particular, cohesin loss causes superenhancers to co-localize, forming hundreds of links within and across chromosomes and affecting the regulation of nearby genes. We then restore cohesin and monitor the re-formation of each loop. Although re-formation rates vary greatly, many megabase-sized loops recovered in under an hour, consistent with a model where loop extrusion is rapid. Mapping the nucleome in 4D during cohesin loss and recovery reveals that cohesin degradation eliminates loop domains but has only modest transcriptional consequences. Keywords: cohesion; genome architecture; loop extrusion; chromatin loops; superenhancers; gene regulation; nuclear compartments; Hi-C; 4D Nucleome; CTCF
MIT Department
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/J.CELL.2017.09.026
