7SK-BAF axis controls pervasive transcription at enhancers.

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.

journal_name

Nat Struct Mol Biol

authors

Flynn RA,Do BT,Rubin AJ,Calo E,Lee B,Kuchelmeister H,Rale M,Chu C,Kool ET,Wysocka J,Khavari PA,Chang HY

doi

10.1038/nsmb.3176

subject

Has Abstract

pub_date

2016-03-01 00:00:00

pages

231-8

issue

3

eissn

1545-9993

issn

1545-9985

pii

nsmb.3176

journal_volume

23

pub_type

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