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Xist RNA antagonizes the SWI/SNF chromatin remodeler BRG1 on the inactive X chromosome.
- Source :
-
Nature structural & molecular biology [Nat Struct Mol Biol] 2019 Feb; Vol. 26 (2), pp. 96-109. Date of Electronic Publication: 2019 Jan 21. - Publication Year :
- 2019
-
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.
- Subjects :
- Adenosine Triphosphatases genetics
Adenosine Triphosphatases metabolism
Animals
Cell Line
Chromatin genetics
Chromosomal Proteins, Non-Histone genetics
Chromosomal Proteins, Non-Histone metabolism
Epigenesis, Genetic genetics
Epigenesis, Genetic physiology
Female
Mice
Nucleosomes genetics
Nucleosomes metabolism
RNA, Long Noncoding genetics
RNA, Untranslated genetics
RNA, Untranslated metabolism
X Chromosome genetics
Chromatin metabolism
RNA, Long Noncoding metabolism
X Chromosome metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1545-9985
- Volume :
- 26
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Nature structural & molecular biology
- Publication Type :
- Academic Journal
- Accession number :
- 30664740
- Full Text :
- https://doi.org/10.1038/s41594-018-0176-8