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Xist RNA antagonizes the SWI/SNF chromatin remodeler BRG1 on the inactive X chromosome.

Abstract：

:The noncoding RNA Xist recruits silencing factors to the inactive X chromosome (Xi) and facilitates re-organization of Xi structure. Here, we examine the mouse epigenomic landscape of Xi and assess how Xist alters chromatin accessibility. Xist deletion triggers a gain of accessibility of select chromatin regions that is regulated by BRG1, an ATPase subunit of the SWI/SNF chromatin-remodeling complex. In vitro, RNA binding inhibits nucleosome-remodeling and ATPase activities of BRG1, while in cell culture Xist directly interacts with BRG1 and expels BRG1 from the Xi. Xist ablation leads to a selective return of BRG1 in cis, starting from pre-existing BRG1 sites that are free of Xist. BRG1 re-association correlates with cohesin binding and restoration of topologically associated domains (TADs) and results in the formation of de novo Xi 'superloops'. Thus, Xist binding inhibits BRG1's nucleosome-remodeling activity and results in expulsion of the SWI/SNF complex from the Xi.

journal_name

Nat Struct Mol Biol

journal_title

Nature structural & molecular biology

authors

Jégu T,Blum R,Cochrane JC,Yang L,Wang CY,Gilles ME,Colognori D,Szanto A,Marr SK,Kingston RE,Lee JT

doi

10.1038/s41594-018-0176-8

subject

Has Abstract

pub_date

2019-02-01 00:00:00

pages

96-109

issue

2

eissn

1545-9993

issn

1545-9985

pii

10.1038/s41594-018-0176-8

journal_volume

26

pub_type

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