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Series GSE72599 Query DataSets for GSE72599
Status Public on Feb 01, 2016
Title 7SK-BAF axis controls pervasive transcription at enhancers [icShape]
Organism Mus musculus
Experiment type Other
Summary Eukaryotic genomes are extensively transcribed, but unfettered transcription alters gene expression and leads to genome damage by several means. Divergent transcription occurs at active enhancers and promoters, distinct classes of cis-regulatory elements critical for precise control of gene expression. A key step in RNA Polymerase II (Pol II) transcription is promoter-proximal pausing, which occurs bidirectionally ~25-60 nucleotides downstream of transcription start sites (TSS). Promoter-proximal pause release is gated by the positive transcription elongation factor b (P-TEFb)-7SK snRNA pathway; release from 7SK allows P-TEFb phosphorylation of Pol II and subsequent elongation. The 7SK small nuclear ribonucleoprotein (snRNP) is thought to reside in the nucleoplasm, but it has been suggested that 7SK could operate physically on chromatin. Notably, while enhancer transcription is one of the earliest steps of gene activation and some enhancer RNAs (eRNAs) participate in gene regulation, far less is known about the control of eRNA transcription. Here we show that 7SK inhibits enhancer transcription by modulating nucleosome position. 7SK occupies enhancers and super enhancers genome-wide, and 7SK is required to limit eRNA initiation and synthesis in a manner distinct from promoter pausing. Clustered elements at super enhancers uniquely require 7SK to prevent convergent transcription of colliding polymerases that lead to DNA damage. 7SK inhibits enhancer transcription by modulating chromatin structure, physically interacts with the BAF chromatin remodeling complex, and is required to recruit BAF to enhancers. In turn, 7SK occupancy at enhancers coincides with Brd4 and is exquisitely sensitive to the bromodomain inhibitor JQ1. Thus, 7SK employs distinct mechanisms to counteract diverse consequences of pervasive transcription that distinguish super enhancers, enhancers, and promoters.
Overall design Each experiment was performed in at least biological duplicate with input or other controls when appropriate.
Contributor(s) Flynn RA, Do BT, Rubin AJ, Calo E, Lee B, Kuchelmeister H, Rale M, Chu C, Kool ET, Wysocka J, Khavari PA, Chang HY
Citation(s) 26878240
Submission date Sep 01, 2015
Last update date May 15, 2019
Contact name Ryan Alexander Flynn
Organization name Stanford University
Street address 380 Roth Way, Room 265
City Stanford
State/province CA
ZIP/Postal code 94305
Country USA
Platforms (1)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (12)
GSM1865836 icSHAPE - mES - BAF coIP - DMSO rep1
GSM1865837 icSHAPE - mES - BAF coIP - DMSO rep2
GSM1865838 icSHAPE - mES - BAF coIP - DMSO rep3
This SubSeries is part of SuperSeries:
GSE69143 7SK-BAF axis controls pervasive transcription at enhancers
BioProject PRJNA294431
SRA SRP063064

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE72599_icSHAPE_reactivity_scores.xlsx 37.2 Kb (ftp)(http) XLSX
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Raw data are available in SRA
Processed data are available on Series record

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