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The structural basis for cohesin-CTCF-anchored loops

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journal contribution
posted on 2020-03-27, 09:57 authored by Yan Li, Judith HI Haarhuis, Angela Sedeno Cacciatore, Roel Oldenkamp, Marjon S van Ruiten, Laureen Willems, Hans Teunissen, Kyle W Muir, Elzo de Wit, Benjamin D Rowland, Daniel Panne
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.

History

Citation

Nature, volume 578, pp.472–476 (2020)

Author affiliation

Leicester Institute of Structural and Chemical Biology, Department of Molecular and Cell Biology

Version

  • AM (Accepted Manuscript)

Published in

NATURE

Volume

578

Issue

7795

Pagination

472-476

Publisher

Nature Research

issn

0028-0836

eissn

1476-4687

Acceptance date

2019-12-05

Copyright date

2020

Publisher version

https://www.nature.com/articles/s41586-019-1910-z

Spatial coverage

England

Language

English