Mediator Condensates Localize Signaling Factors to Key Cell Identity Genes
Name
nihms-1538552.pdf
Description
Accepted version
Size
2.13 MB
Format
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Checksum (MD5)
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Author(s)
Zamudio Montes de Oca, Alicia
Dall’Agnese, Alessandra
Henninger, Jonathan E.
Manteiga, John Colonnese
Afeyan, Lena K.
Hannett, Nancy M.
Coffey, Eliot Leo
Li, Charles Han
Oksuz, Ozgur
Sabari, Benjamin R.
Date Issued
December 2019
Journal
Molecular Cell
Publisher
Elsevier BV
Citation
Zamudio, Alicia V. et al. “Mediator Condensates Localize Signaling Factors to Key Cell Identity Genes.” Molecular Cell, 76, 5 (December 2019): 753–766.e6 © 2019 The Author(s)
Version
Author's final manuscript
Abstract
The gene expression programs that define the identity of each cell are controlled by master transcription factors (TFs) that bind cell-type-specific enhancers, as well as signaling factors, which bring extracellular stimuli to these enhancers. Recent studies have revealed that master TFs form phase-separated condensates with the Mediator coactivator at super-enhancers. Here, we present evidence that signaling factors for the WNT, TGF-β, and JAK/STAT pathways use their intrinsically disordered regions (IDRs) to enter and concentrate in Mediator condensates at super-enhancers. We show that the WNT coactivator β-catenin interacts both with components of condensates and DNA-binding factors to selectively occupy super-enhancer-associated genes. We propose that the cell-type specificity of the response to signaling is mediated in part by the IDRs of the signaling factors, which cause these factors to partition into condensates established by the master TFs and Mediator at genes with prominent roles in cell identity.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Physics
Whitehead Institute for Biomedical Research
Massachusetts Institute of Technology. Computational and Systems Biology Program
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/J.MOLCEL.2019.08.016
