Cohesin is positioned in mammalian genomes by transcription, CTCF and Wapl

Mammalian genomes are spatially organized by CCCTC-binding factor (CTCF) and cohesin into chromatin loops and topologically associated domains, which have important roles in gene regulation and recombination. By binding to specific sequences, CTCF defines contact points for cohesin-mediated long-ran...

Full description

Saved in:
Bibliographic Details
Published in:Nature (London) 2017-04, Vol.544 (7651), p.503-507
Main Authors: Busslinger, Georg A, Stocsits, Roman R, van der Lelij, Petra, Axelsson, Elin, Tedeschi, Antonio, Galjart, Niels, Peters, Jan-Michael
Format: Article
Language:English
Subjects:
Animals
Binding Sites
CCCTC-Binding Factor
Cell Cycle Proteins - deficiency
Cell Cycle Proteins - genetics
Cell Cycle Proteins - metabolism
Cells, Cultured
Chondroitin Sulfate Proteoglycans - deficiency
Chondroitin Sulfate Proteoglycans - genetics
Chromatin - genetics
Chromatin - metabolism
Chromosomal Proteins, Non-Histone - deficiency
Chromosomal Proteins, Non-Histone - genetics
Chromosomal Proteins, Non-Histone - metabolism
Chromosomes, Mammalian - genetics
Chromosomes, Mammalian - metabolism
Cohesins
Deoxyribonucleic acid
DNA
DNA - genetics
DNA - metabolism
Experiments
Female
Fibroblasts - cytology
Fibroblasts - metabolism
Gene expression
Genome - genetics
Genomes
Localization
Male
Mice
Protein Transport
Proteins - genetics
Proteins - metabolism
Repressor Proteins - deficiency
Repressor Proteins - genetics
Repressor Proteins - metabolism
Transcription Initiation Site
Transcription, Genetic - genetics
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Mammalian genomes are spatially organized by CCCTC-binding factor (CTCF) and cohesin into chromatin loops and topologically associated domains, which have important roles in gene regulation and recombination. By binding to specific sequences, CTCF defines contact points for cohesin-mediated long-range chromosomal cis-interactions. Cohesin is also present at these sites, but has been proposed to be loaded onto DNA elsewhere and to extrude chromatin loops until it encounters CTCF bound to DNA. How cohesin is recruited to CTCF sites, according to this or other models, is unknown. Here we show that the distribution of cohesin in the mouse genome depends on transcription, CTCF and the cohesin release factor Wings apart-like (Wapl). In CTCF-depleted fibroblasts, cohesin cannot be properly recruited to CTCF sites but instead accumulates at transcription start sites of active genes, where the cohesin-loading complex is located. In the absence of both CTCF and Wapl, cohesin accumulates in up to 70 kilobase-long regions at 3'-ends of active genes, in particular if these converge on each other. Changing gene expression modulates the position of these 'cohesin islands'. These findings indicate that transcription can relocate mammalian cohesin over long distances on DNA, as previously reported for yeast cohesin, that this translocation contributes to positioning cohesin at CTCF sites, and that active genes can be freed from cohesin either by transcription-mediated translocation or by Wapl-mediated release.
ISSN:0028-0836
1476-4687
DOI:10.1038/nature22063