ESCO1 and CTCF enable formation of long chromatin loops by protecting cohesinSTAG1 from WAPL

Gordana Wutz, Rene Ladurner, Brian St Hilaire, Roman Stocsits, Kota Nagasaka, Benoit Pignard, Adrian Sanborn, Wen Tang, Csilla Várnai, Miroslav Ivanov, Stefan Schoenfelder, Petra van der Lelij, Xingfan Huang, Gerhard Dürnberger, Elisabeth Roitinger, Karl Mechtler, Iain F. Davidson, Peter Fraser, Erez Lieberman Aiden, Jan-Michael Peters

Research output: Other contribution

Abstract

Eukaryotic genomes are folded into loops. It is thought that these are formed by cohesin complexes via extrusion, either until loop expansion is arrested by CTCF or until cohesin is removed from DNA by WAPL. Although WAPL limits cohesin’s chromatin residence time to minutes, it has been reported that some loops exist for hours. How these loops can persist is unknown. We show that during G1-phase, mammalian cells contain acetylated cohesinSTAG1 which binds chromatin for hours, whereas cohesinSTAG2 binds chromatin for minutes. Our results indicate that CTCF and the acetyltransferase ESCO1 protect a subset of cohesinSTAG1 complexes from WAPL, thereby enable formation of long and presumably long-lived loops, and that ESCO1, like CTCF, contributes to boundary formation in chromatin looping. Our data are consistent with a model of nested loop extrusion, in which acetylated cohesinSTAG1 forms stable loops between CTCF sites, demarcating the boundaries of more transient cohesinSTAG2 extrusion activity.
Original languageEnglish
DOIs
Publication statusPublished - 23 Sep 2019

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