Transcription Factors Activate Genes through the Phase-Separation Capacity of Their Activation Domains.

Autor:	Boija A; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA., Klein IA; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA., Sabari BR; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA., Dall'Agnese A; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA., Coffey EL; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA., Zamudio AV; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA., Li CH; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA., Shrinivas K; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Institute of Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA., Manteiga JC; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA., Hannett NM; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA., Abraham BJ; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA., Afeyan LK; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA., Guo YE; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA., Rimel JK; Department of Biochemistry, University of Colorado, Boulder, CO 80303, USA., Fant CB; Department of Biochemistry, University of Colorado, Boulder, CO 80303, USA., Schuijers J; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA., Lee TI; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA., Taatjes DJ; Department of Biochemistry, University of Colorado, Boulder, CO 80303, USA., Young RA; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: young@wi.mit.edu.
Jazyk:	angličtina
Zdroj:	Cell [Cell] 2018 Dec 13; Vol. 175 (7), pp. 1842-1855.e16. Date of Electronic Publication: 2018 Nov 15.
DOI:	10.1016/j.cell.2018.10.042
Abstrakt:	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. (Copyright © 2018 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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