RT Journal Article
SR Electronic
T1 Cohesin loss eliminates all loop domains, leading to links among superenhancers and downregulation of nearby genes
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 139782
DO 10.1101/139782
A1 Suhas S. P. Rao
A1 Su-Chen Huang
A1 Brian Glenn St Hilair
A1 Jesse M. Engreitz
A1 Elizabeth M. Perez
A1 Kyong-Rim Kieffer-Kwon
A1 Adrian L. Sanborn
A1 Sarah E. Johnstone
A1 Ivan D. Bochkov
A1 Xingfan Huang
A1 Muhammad S. Shamim
A1 Arina D. Omer
A1 Bradley E. Bernstein
A1 Rafael Casellas
A1 Eric S. Lander
A1 Erez Lieberman Aiden
YR 2017
UL http://biorxiv.org/content/early/2017/05/18/139782.abstract
AB 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. Loci in different compartments that had been in the same loop domain become more segregated. 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. Cohesin restoration quickly reverses these effects, consistent with a model where loop extrusion is rapid.