Cohesin Loss Eliminates All Loop Domains
| Autor: | Gavin D. Bascom, Jesse M. Engreitz, Douglass Turner, Elizabeth M. Perez, James T. Robinson, Tamar Schlick, Muhammad S. Shamim, Jaeweon Shin, Arina D. Omer, Rafael Casellas, Kyong-Rim Kieffer-Kwon, Erez Lieberman Aiden, Sarah E. Johnstone, Bradley E. Bernstein, Eric S. Lander, Xingfan Huang, Ziyi Ye, Adrian L. Sanborn, Ivan D. Bochkov, Brian Glenn St Hilaire, Su Chen Huang, Suhas S.P. Rao |
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| Přispěvatelé: | Massachusetts Institute of Technology. Department of Biology, Lander, Eric Steven |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
CCCTC-Binding Factor Chromosomal Proteins Non-Histone Cell Cycle Proteins Biology Article Chromosomes General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Cell Line Tumor Humans Nucleosome Histone code Compartment (development) Cell Nucleus Genetics Regulation of gene expression Cohesin Genome Human Nuclear Proteins Phosphoproteins Nucleosomes Cell biology DNA-Binding Proteins Histone Code Repressor Proteins Enhancer Elements Genetic 030104 developmental biology Histone CTCF biology.protein Chromatin Loop biological phenomena cell phenomena and immunity |
| Zdroj: | PMC |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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