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 Bioljournal_title
Nature structural & molecular biologyauthors
Flynn RA,Do BT,Rubin AJ,Calo E,Lee B,Kuchelmeister H,Rale M,Chu C,Kool ET,Wysocka J,Khavari PA,Chang HYdoi
10.1038/nsmb.3176subject
Has Abstractpub_date
2016-03-01 00:00:00pages
231-8issue
3eissn
1545-9993issn
1545-9985pii
nsmb.3176journal_volume
23pub_type
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