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| Status |
Public on Feb 01, 2016 |
| Title |
7SK-BAF axis controls pervasive transcription at enhancers [icShape] |
| Organism |
Mus musculus |
| Experiment type |
Other
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| 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.
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| Overall design |
Each experiment was performed in at least biological duplicate with input or other controls when appropriate.
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| 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 |
| E-mail(s) |
raflynn@stanford.edu
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| Organization name |
Stanford University
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| Street address |
380 Roth Way, Room 265
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| City |
Stanford |
| State/province |
CA |
| ZIP/Postal code |
94305 |
| Country |
USA |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (12)
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| GSM1865839 |
icSHAPE - mES - BAF coIP - NAI-N3 rep1 |
| GSM1865840 |
icSHAPE - mES - BAF coIP - NAI-N3 rep2 |
| GSM1865841 |
icSHAPE - mES - BAF coIP - NAI-N3 rep3 |
| GSM1865842 |
icSHAPE - mES - Hexim1 coIP - DMSO rep1 |
| GSM1865843 |
icSHAPE - mES - Hexim1 coIP - DMSO rep2 |
| GSM1865844 |
icSHAPE - mES - Hexim1 coIP - DMSO rep3 |
| GSM1865845 |
icSHAPE - mES - Hexim1 coIP - NAI-N3 rep1 |
| GSM1865846 |
icSHAPE - mES - Hexim1 coIP - NAI-N3 rep2 |
| GSM1865847 |
icSHAPE - mES - Hexim1 coIP - NAI-N3 rep3 |
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| This SubSeries is part of SuperSeries: |
| GSE69143 |
7SK-BAF axis controls pervasive transcription at enhancers |
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| Relations |
| BioProject |
PRJNA294431 |
| SRA |
SRP063064 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE72599_icSHAPE_reactivity_scores.xlsx |
37.2 Kb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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