Mediator and RNA polymerase II clusters associate in transcription-dependent condensates
Won-Ki Cho,Jan-Hendrik Spille,Micca Hecht,Choongman Lee,Charles H. Li,Valentin Grube,Valentin Grube,Ibrahim I Cisse +7 more
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TLDR
This work used live-cell superresolution and light-sheet imaging to study the organization and dynamics of the Mediator coactivator and RNA polymerase II (Pol II) directly and suggests that large clusters of Mediator, recruited by transcription factors at large or clustered enhancer elements, interact with large Pol II clusters in transcriptional condensates in vivo.Abstract:
Models of gene control have emerged from genetic and biochemical studies, with limited consideration of the spatial organization and dynamics of key components in living cells. We used live-cell superresolution and light-sheet imaging to study the organization and dynamics of the Mediator coactivator and RNA polymerase II (Pol II) directly. Mediator and Pol II each form small transient and large stable clusters in living embryonic stem cells. Mediator and Pol II are colocalized in the stable clusters, which associate with chromatin, have properties of phase-separated condensates, and are sensitive to transcriptional inhibitors. We suggest that large clusters of Mediator, recruited by transcription factors at large or clustered enhancer elements, interact with large Pol II clusters in transcriptional condensates in vivo.read more
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An order-to-disorder structural switch activates the FoxM1 transcription factor.
Aimee H. Marceau,Caileen M Brison,Santrupti Nerli,Heather E. Arsenault,Andrew C. McShan,Eefei Chen,Hsiau-Wei Lee,Jennifer A. Benanti,Nikolaos G. Sgourakis,Seth M. Rubin +9 more
TL;DR: This work identifies how Plk1 and Cdk kinases cooperate to phosphorylate FoxM1, which releases the TAD into a disordered conformation that then associates with the TAZ2 or KIX domains of the transcriptional co-activator CBP.
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A revised model for promoter competition based on multi-way chromatin interactions
TL;DR: These finding show that promoters within the same domain do not structurally compete for interactions with enhancers, but form a regulatory hub structure, consistent with the recent model of transcriptional activation in phase-separated nuclear condensates.
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Computational approaches from polymer physics to investigate chromatin folding.
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