Coactivator condensation at super-enhancers links phase separation and gene control
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nihms-983922.pdf
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Author(s)
Sabari, Benjamin R.
Dall’Agnese, Alessandra
Boija, Ann
Klein, Isaac A.
Abraham, Brian J.
Hannett, Nancy M.
Guo, Yang E.
Day, Daniel S.
Schuijers, Jurian
Hnisz, Denes
Date Issued
July 2018
Journal
Science
Publisher
American Association for the Advancement of Science (AAAS)
Citation
Sabari, Benjamin R. et al. “Coactivator Condensation at Super-Enhancers Links Phase Separation and Gene Control.” Science 361, 6400 (June 2018): eaar3958 © 2018 The Authors
Version
Author's final manuscript
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Chemical Engineering
Massachusetts Institute of Technology. Department of Chemistry
Massachusetts Institute of Technology. Department of Physics
Koch Institute for Integrative Cancer Research at MIT
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DOI of Published Version
https://doi.org/10.1126/science.aar3958
