TY - JOUR T1 - Cohesin loss eliminates all loop domains, leading to links among superenhancers and downregulation of nearby genes JF - bioRxiv DO - 10.1101/139782 SP - 139782 AU - Suhas S. P. Rao AU - Su-Chen Huang AU - Brian Glenn St Hilair AU - Jesse M. Engreitz AU - Elizabeth M. Perez AU - Kyong-Rim Kieffer-Kwon AU - Adrian L. Sanborn AU - Sarah E. Johnstone AU - Ivan D. Bochkov AU - Xingfan Huang AU - Muhammad S. Shamim AU - Arina D. Omer AU - Bradley E. Bernstein AU - Rafael Casellas AU - Eric S. Lander AU - Erez Lieberman Aiden Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/05/18/139782.abstract N2 - 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. ER -