@article{7ca107a503a740aa8319539f4b50e77a,
title = "Transcription Factors Activate Genes through the Phase-Separation Capacity of Their Activation Domains",
abstract = "Gene expression is controlled by transcription factors (TFs) that consist of DNA-binding domains (DBDs) and activation domains (ADs). The DBDs have been well characterized, but little is known about the mechanisms by which ADs effect gene activation. Here, we report that diverse ADs form phase-separated condensates with the Mediator coactivator. For the OCT4 and GCN4 TFs, we show that the ability to form phase-separated droplets with Mediator in vitro and the ability to activate genes in vivo are dependent on the same amino acid residues. For the estrogen receptor (ER), a ligand-dependent activator, we show that estrogen enhances phase separation with Mediator, again linking phase separation with gene activation. These results suggest that diverse TFs can interact with Mediator through the phase-separating capacity of their ADs and that formation of condensates with Mediator is involved in gene activation.",
keywords = "activation domain, gene activation, mediator, phase separation, transcription, transcription factor",
author = "Ann Boija and Klein, {Isaac A.} and Sabari, {Benjamin R.} and Alessandra Dall'Agnese and Coffey, {Eliot L.} and Zamudio, {Alicia V.} and Li, {Charles H.} and Krishna Shrinivas and Manteiga, {John C.} and Hannett, {Nancy M.} and Abraham, {Brian J.} and Afeyan, {Lena K.} and Guo, {Yang E.} and Rimel, {Jenna K.} and Fant, {Charli B.} and Jurian Schuijers and Lee, {Tong Ihn} and Taatjes, {Dylan J.} and Young, {Richard A.}",
note = "Funding Information: We thank Wendy Salmon of the W.M. Keck Microscopy Facility, the Whitehead Genomics Core, Arup Chakraborty, and Philip A. Sharp. The work was supported by NIH grant GM123511 and NSF grant PHY1743900 (R.A.Y.), NIH grant GM117370 (D.J.T.), Swedish Research Council Postdoctoral Fellowship ( VR 2017-00372 ) (A.B.), NIH grant T32CA009172 (I.A.K.), a Damon Runyon Cancer Research Foundation Fellowship ( 2309-17 ) (B.R.S.), a NSF Graduate Research Fellowship (A.V.Z.), a Hope Funds for Cancer Research fellowship (B.J.A.), a Cancer Research Institute Irvington Fellowship (Y.E.G.), NIH grant T32GM08759 (C.B.F.), and a NWO Rubicon Fellowship (J.S.). Funding Information: We thank Wendy Salmon of the W.M. Keck Microscopy Facility, the Whitehead Genomics Core, Arup Chakraborty, and Philip A. Sharp. The work was supported by NIH grant GM123511 and NSF grant PHY1743900 (R.A.Y.), NIH grant GM117370 (D.J.T.), Swedish Research Council Postdoctoral Fellowship (VR 2017-00372) (A.B.), NIH grant T32CA009172 (I.A.K.), a Damon Runyon Cancer Research Foundation Fellowship (2309-17) (B.R.S.), a NSF Graduate Research Fellowship (A.V.Z.), a Hope Funds for Cancer Research fellowship (B.J.A.), a Cancer Research Institute Irvington Fellowship (Y.E.G.), NIH grant T32GM08759 (C.B.F.), and a NWO Rubicon Fellowship (J.S.). Publisher Copyright: {\textcopyright} 2018 Elsevier Inc.",
year = "2018",
month = dec,
day = "13",
doi = "10.1016/j.cell.2018.10.042",
language = "English (US)",
volume = "175",
pages = "1842--1855.e16",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "7",
}