Journal
SCIENCE
Volume 361, Issue 6400, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aar3958
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Funding
- NIH [GM123511, P01-CA042063]
- NSF [PHY-1743900]
- NCI [P30-CA14051]
- Damon Runyon Cancer Research Foundation Fellowship [2309-17]
- Swedish Research Council Postdoctoral Fellowship [VR 2017-00372]
- Hope Funds for Cancer Research fellowship
- NSF Graduate Research Fellowship
- Cancer Research Institute Irvington Fellowship
- American Cancer Society New England Division Postdoctoral Fellowship [PF-16-146-01-DMC]
- NWO Rubicon Fellowship
- Swedish Research Council [2017-00372] Funding Source: Swedish Research Council
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Super-enhancers (SEs) are clusters of enhancers that cooperatively assemble a high density of the transcriptional apparatus to drive robust expression of genes with prominent roles in cell identity. Here we demonstrate that the SE-enriched transcriptional coactivators BRD4 and MED1 form nuclear puncta at SEs that exhibit properties of liquid-like condensates and are disrupted by chemicals that perturb condensates. The intrinsically disordered regions (IDRs) of BRD4 and MED1 can form phase-separated droplets, and MED1-IDR droplets can compartmentalize and concentrate the transcription apparatus from nuclear extracts. These results support the idea that coactivators form phase-separated condensates at SEs that compartmentalize and concentrate the transcription apparatus, suggest a role for coactivator IDRs in this process, and offer insights into mechanisms involved in the control of key cell-identity genes.
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