Affordable Access

deepdyve-link
Publisher Website

The structural basis for cohesin-CTCF-anchored loops.

Authors
  • Li, Yan1
  • Haarhuis, Judith H I2
  • Sedeño Cacciatore, Ángela2
  • Oldenkamp, Roel2
  • van Ruiten, Marjon S2
  • Willems, Laureen2
  • Teunissen, Hans3
  • Muir, Kyle W4, 5
  • de Wit, Elzo6
  • Rowland, Benjamin D7
  • Panne, Daniel8, 9
  • 1 European Molecular Biology Laboratory, Grenoble, France. , (France)
  • 2 Division of Gene Regulation, The Netherlands Cancer Institute, Amsterdam, The Netherlands. , (Netherlands)
  • 3 Division of Gene Regulation, Oncode Institute, The Netherlands Cancer Institute, Amsterdam, The Netherlands. , (Netherlands)
  • 4 European Molecular Biology Laboratory, Grenoble, France. [email protected] , (France)
  • 5 MRC Laboratory of Molecular Biology, Cambridge, UK. [email protected]
  • 6 Division of Gene Regulation, Oncode Institute, The Netherlands Cancer Institute, Amsterdam, The Netherlands. [email protected] , (Netherlands)
  • 7 Division of Gene Regulation, The Netherlands Cancer Institute, Amsterdam, The Netherlands. [email protected] , (Netherlands)
  • 8 European Molecular Biology Laboratory, Grenoble, France. [email protected] , (France)
  • 9 Leicester Institute of Structural and Chemical Biology, Department of Molecular and Cell Biology, University of Leicester, Leicester, UK. [email protected]
Type
Published Article
Journal
Nature
Publisher
Springer Nature
Publication Date
Feb 01, 2020
Volume
578
Issue
7795
Pages
472–476
Identifiers
DOI: 10.1038/s41586-019-1910-z
PMID: 31905366
Source
Medline
Language
English
License
Unknown

Abstract

Cohesin catalyses the folding of the genome into loops that are anchored by CTCF1. The molecular mechanism of how cohesin and CTCF structure the 3D genome has remained unclear. Here we show that a segment within the CTCF N terminus interacts with the SA2-SCC1 subunits of human cohesin. We report a crystal structure of SA2-SCC1 in complex with CTCF at a resolution of 2.7 Å, which reveals the molecular basis of the interaction. We demonstrate that this interaction is specifically required for CTCF-anchored loops and contributes to the positioning of cohesin at CTCF binding sites. A similar motif is present in a number of established and newly identified cohesin ligands, including the cohesin release factor WAPL2,3. Our data suggest that CTCF enables the formation of chromatin loops by protecting cohesin against loop release. These results provide fundamental insights into the molecular mechanism that enables the dynamic regulation of chromatin folding by cohesin and CTCF.

Report this publication

Statistics

Seen <100 times