PT  - JOURNAL ARTICLE
AU  - Wutz, Gordana
AU  - Ladurner, Rene
AU  - St. Hilaire, Brian
AU  - Stocsits, Roman
AU  - Nagasaka, Kota
AU  - Pignard, Benoit
AU  - Sanborn, Adrian
AU  - Tang, Wen
AU  - Várnai, Csilla
AU  - Ivanov, Miroslav
AU  - Schoenfelder, Stefan
AU  - van der Lelij, Petra
AU  - Huang, Xingfan
AU  - Dürnberger, Gerhard
AU  - Roitinger, Elisabeth
AU  - Mechtler, Karl
AU  - Davidson, Iain F.
AU  - Fraser, Peter
AU  - Aiden, Erez Lieberman
AU  - Peters, Jan-Michael
TI  - ESCO1 and CTCF enable formation of long chromatin loops by protecting cohesin<sup>STAG1</sup> from WAPL
AID  - 10.1101/779058
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 779058
4099  - http://biorxiv.org/content/early/2019/09/23/779058.short
4100  - http://biorxiv.org/content/early/2019/09/23/779058.full
AB  - 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.