Mediator Condensates Localize Signaling Factors to Key Cell Identity Genes
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.; Boija, Ann; Klein, Isaac A.; Hawken, Susana W; Spille, Jan Hendrik; Cisse, Ibrahim I; Abraham, Brian Joseph; Lee, Tong Ihn; Taatjes, Dylan J.; Schuijers, Jurian; Young, Richard A.; ... Show more Show less
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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.
DepartmentMassachusetts 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
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)
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