Coactivator condensation at super-enhancers links phase separation and gene controlстатья из журнала
Аннотация: 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.
Год издания: 2018
Авторы: Benjamin R. Sabari, Alessandra Dall’Agnese, Ann Boija, Isaac A. Klein, Eliot L. Coffey, Krishna Shrinivas, Brian J. Abraham, Nancy M. Hannett, Alicia V. Zamudio, John C. Manteiga, Charles H. Li, Yang Guo, Daniel S. Day, Jurian Schuijers, Eliza Vasile, Sohail Malik, Denes Hnisz, Tong Ihn Lee, I. Cissé, Robert G. Roeder, Phillip A. Sharp, Arup K. Chakraborty, Richard A. Young
Издательство: American Association for the Advancement of Science
Источник: Science
Ключевые слова: Genomics and Chromatin Dynamics, RNA Research and Splicing, Protein Degradation and Inhibitors
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