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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Apr 07, 2018 |
| Title |
Coactivator condensation at super-enhancers links phase separation and gene control (RNA-Seq) |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Super-enhancers (SEs) are clusters of enhancers that cooperatively assemble a high density of transcriptional apparatus to drive robust expression of genes with prominent roles in cell identity. We recently proposed that a phase-separated multi-molecular assembly underlies the formation and function of SEs. Here, we demonstrate that the SE-enriched factors BRD4 and MED1 form nuclear puncta that occur at SEs and exhibit properties of liquid-like condensates. Disruption of BRD4 and MED1 puncta by 1,6-hexanediol is accompanied by a loss of BRD4 and MED1 at SEs and a loss of RNAPII from SE-driven genes. We find that the intrinsically disordered regions (IDRs) of BRD4 and MED1 are sufficient to form phase-separated droplets in vitro and the MED1 IDR promotes phase separation in living cells. The MED1 IDR droplets are capable of compartmentalizing BRD4 and other transcriptional machinery in nuclear extracts. These results support the idea that SEs form phase-separated condensates that compartmentalize the transcription apparatus at key genes, provide insights into the role of cofactor IDRs in this process, and offer new insights into mechanisms involved in control of key cell identity genes.
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| Overall design |
polyA RNA-Seq in mouse embryonic stem cells
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| Contributor(s) |
Sabari BR, Dall'Agnese A, Boija A, Klein I, Coffey EL, Shrinivas K, Abraham BJ, Hannett NM, Zamudia AV, Manteiga JC, Li CH, Day DS, Schuijers J, Vasile E, Malik S, Lee TI, Cisse II, Roeder RG, Sharp PA, Chakraborty AK, Young RA |
| Citation(s) |
29930091 |
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| Submission date |
Apr 06, 2018 |
| Last update date |
Mar 21, 2019 |
| Contact name |
Richard A Young |
| E-mail(s) |
young_computation@wi.mit.edu
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| Phone |
617-258-5219
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| Organization name |
Whitehead Institute for Biomedical Research
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| Lab |
Young Lab
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| Street address |
9 Cambridge Center
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| City |
Cambridge |
| State/province |
MA |
| ZIP/Postal code |
02142 |
| Country |
USA |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (2) |
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| This SubSeries is part of SuperSeries: |
| GSE112808 |
Coactivator condensation at super-enhancers links phase separation and gene control |
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| Relations |
| BioProject |
PRJNA449067 |
| SRA |
SRP137822 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE112807_RAW.tar |
530.0 Kb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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