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Nat Struct Mol Biol. 2016 Mar;23(3):231-8. doi: 10.1038/nsmb.3176. Epub 2016 Feb 15.

7SK-BAF axis controls pervasive transcription at enhancers.

Author information

1
Center for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, California, USA.
2
Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California, USA.
3
Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, California, USA.
4
Department of Chemistry, Stanford University, Stanford, California, USA.
5
The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, USA.

Abstract

RNA functions at enhancers remain mysterious. Here we show that the 7SK small nuclear RNA (snRNA) inhibits enhancer transcription by modulating nucleosome position. 7SK occupies enhancers and super enhancers genome wide in mouse and human cells, and it is required to limit enhancer-RNA initiation and synthesis in a manner distinct from promoter pausing. Clustered elements at super enhancers uniquely require 7SK to prevent convergent transcription and DNA-damage signaling. 7SK physically interacts with the BAF chromatin-remodeling complex, recruits BAF to enhancers and inhibits enhancer transcription by modulating chromatin structure. In turn, 7SK occupancy at enhancers coincides with that of Brd4 and is exquisitely sensitive to the bromodomain inhibitor JQ1. Thus, 7SK uses distinct mechanisms to counteract the diverse consequences of pervasive transcription that distinguish super enhancers, enhancers and promoters.

PMID:
26878240
PMCID:
PMC4982704
DOI:
10.1038/nsmb.3176
[Indexed for MEDLINE]
Free PMC Article

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