title: 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.
authors.affiliation: Center for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, California, USA.|Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Ryan A
authors.identifier: http://orcid.org/0000-0001-5013-0442
authors.initials: RA
authors.lastname: Flynn
authors.affiliation: Center for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, California, USA.|Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Do
authors.affiliation: Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Rubin
authors.affiliation: Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Eliezer
authors.initials: E
authors.lastname: Calo
authors.affiliation: Center for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, California, USA.|Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Byron
authors.initials: B
authors.lastname: Lee
authors.affiliation: Department of Chemistry, Stanford University, Stanford, California, USA.
authors.forename: Hannes
authors.initials: H
authors.lastname: Kuchelmeister
authors.affiliation: The Genome Institute, Washington University in St. Louis, St. Louis, Missouri, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Rale
authors.affiliation: Center for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, California, USA.|Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Ci
authors.initials: C
authors.lastname: Chu
authors.affiliation: Department of Chemistry, Stanford University, Stanford, California, USA.
authors.forename: Eric T
authors.initials: ET
authors.lastname: Kool
authors.affiliation: Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Joanna
authors.initials: J
authors.lastname: Wysocka
authors.affiliation: Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Khavari
authors.affiliation: Center for Personal Dynamic Regulomes, Stanford University School of Medicine, Stanford, California, USA.|Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Howard Y
authors.initials: HY
authors.lastname: Chang
mesh_terms: D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D009707:Nucleosomes / Q000378:metabolism*; D012342:RNA, Small Nuclear / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D004268:DNA-Binding Proteins; D009707:Nucleosomes; D012342:RNA, Small Nuclear