Coactivator condensation at super-enhancers links phase separation and gene control | Zendy

Benjamin R. Sabari | Zendy; Alessandra Dall’Agnese | Zendy; Ann Boija | Zendy; Isaac A. Klein | Zendy; Eliot L. Coffey | Zendy; Krishna Shrinivas | Zendy; Brian J. Abraham | Zendy; Nancy M. Hannett | Zendy; Alicia V. Zamudio | Zendy; John C. Manteiga | Zendy; Charles H. Li | Zendy; Yang Guo | Zendy; Daniel S. Day | Zendy; Jurian Schuijers | Zendy; Eliza Vasile | Zendy; Sohail Malik | Zendy; Denes Hnisz | Zendy; Tong Ihn Lee | Zendy; I. Cissé | Zendy; Robert G. Roeder | Zendy; Phillip A. Sharp | Zendy; Arup K. Chakraborty | Zendy; Richard A. Young | Zendy

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Coactivator condensation at super-enhancers links phase separation and gene control

Author(s) -

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

Publication year - 2018

Publication title -

science

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 12.556

H-Index - 1186

eISSN - 1095-9203

pISSN - 0036-8075

DOI - 10.1126/science.aar3958

Subject(s) - coactivator , enhancer , transcription (linguistics) , microbiology and biotechnology , transcription factor , intrinsically disordered proteins , gene , biology , chemistry , biophysics , genetics , linguistics , philosophy

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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