Coactivator condensation at super-enhancers links phase separation and gene control
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; Lee, Tong Ihn; Coffey, Eliot Leo; Shrinivas, Krishna; Zamudio Montes de Oca, Alicia; Manteiga, John Colonnese; Li, Charles Han; Vasile, Eliza; Cisse, Ibrahim I; Sharp, Phillip A; Chakraborty, Arup K; Young, Richard A; ... Show more Show less
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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.
DepartmentInstitute for Medical Engineering and Science; David H. Koch Institute for Integrative Cancer Research at MIT; 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
American Association for the Advancement of Science (AAAS)
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
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