| Literature DB >> 29930091 |
Benjamin R Sabari1, Alessandra Dall'Agnese1, Ann Boija1, Isaac A Klein1,2, Eliot L Coffey1,3, Krishna Shrinivas4,5, Brian J Abraham1, Nancy M Hannett1, Alicia V Zamudio1,3, John C Manteiga1,3, Charles H Li1,3, Yang E Guo1, Daniel S Day1, Jurian Schuijers1, Eliza Vasile6, Sohail Malik7, Denes Hnisz1, Tong Ihn Lee1, Ibrahim I Cisse8, Robert G Roeder7, Phillip A Sharp3,6, Arup K Chakraborty4,5,8,9,10,11, Richard A Young12,3.
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.Entities:
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Year: 2018 PMID： 29930091 PMCID： PMC6092193 DOI： 10.1126/science.aar3958
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728