Transcription Factors Activate Genes through the Phase-Separation Capacity of Their Activation Domains
Name
nihms-1510266.pdf
Description
Accepted version
Size
1.03 MB
Format
Adobe PDF
Checksum (MD5)
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Author(s)
Klein, Isaac A.
Sabari, Benjamin R.
Dall’Agnese, Alessandra
Coffey, Eliot L.
Zamudio, Alicia V.
Manteiga, John C.
Hannett, Nancy M.
Abraham, Brian J.
Afeyan, Lena K.
Guo, Yang E.
Date Issued
December 2018
Journal
Cell
Publisher
Elsevier BV
Citation
Boijja, Ann et al. "Transcription Factors Activate Genes through the Phase-Separation Capacity of Their Activation Domains." Cell 175 (2018): 1842-1855 © 2019 The Author(s)
Version
Author's final manuscript
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.
Subjects
General Biochemistry, Genetics and Molecular Biology
MIT Department
Whitehead Institute for Biomedical Research
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Chemical Engineering
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
10.1016/j.cell.2018.10.042
