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Nature. 2020 Jan 6. doi: 10.1038/s41586-019-1910-z. [Epub ahead of print]

The structural basis for cohesin-CTCF-anchored loops.

Author information

1
European Molecular Biology Laboratory, Grenoble, France.
2
Division of Gene Regulation, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
3
Oncode Institute, Utrecht, The Netherlands.
4
European Molecular Biology Laboratory, Grenoble, France. kmuir@mrc-lmb.cam.ac.uk.
5
MRC Laboratory of Molecular Biology, Cambridge, UK. kmuir@mrc-lmb.cam.ac.uk.
6
Division of Gene Regulation, The Netherlands Cancer Institute, Amsterdam, The Netherlands. e.d.wit@nki.nl.
7
Oncode Institute, Utrecht, The Netherlands. e.d.wit@nki.nl.
8
Division of Gene Regulation, The Netherlands Cancer Institute, Amsterdam, The Netherlands. b.rowland@nki.nl.
9
European Molecular Biology Laboratory, Grenoble, France. daniel.panne@le.ac.uk.
10
Leicester Institute of Structural and Chemical Biology, Department of Molecular and Cell Biology, University of Leicester, Leicester, UK. daniel.panne@le.ac.uk.

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 cohesin. A 2.6 Å crystal structure of SA2-SCC1 in complex with CTCF 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 novel cohesin ligands, including the cohesin release factor WAPL2,3. Our data suggest that CTCF enables chromatin loop formation by protecting cohesin against loop release. These results provide fundamental insights into the molecular mechanism that enables dynamic regulation of chromatin folding by cohesin and CTCF.

PMID:
31905366
DOI:
10.1038/s41586-019-1910-z

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