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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Mediator complex subunit Med19 binds directly GATA DNA-binding zinc finger and functions with Med1 in GATA-driven gene regulation in vivo
Clément Immarigeon,Sandra Bernat-Fabre,Emmanuelle Guillou,Alexis Verger,Elodie Prince,Mohamed A. Benmedjahed,Adeline Payet,Marie Couralet,Didier Monté,Vincent Villeret,Henri-Marc Bourbon,Muriel Boube +11 more
TL;DR: New light is shed on the MED complex, engaging several subunits to mediate TF-driven transcriptional responses and second, on GATA TFs, showing that ZF DNA-binding domain also serves for transactivation.
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Distinguishing between models of mammalian gene expression: telegraph-like models versus mechanistic models
TL;DR: In this article, the authors compare two-state models and a stochastic mechanistic model of transcription in mammalian cells and identify a means to select between them from experimental data.
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BRD4-targeting PROTAC as a unique tool to study biomolecular condensates
TL;DR: In this paper , a BRD4-targeting PROTAC molecule was used to regulate the super-enhancer (SE) condensate and monitored the changes of SE-condensate under PROTAC treatment using live-cell imaging and high-throughput sequencing technologies.
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Transcription factor clusters enable target search but do not contribute to target gene activation
TL;DR: In this paper , the authors used quantitative microscopy in living cells to study the regulation and function of clustering of the budding yeast TF Gal4 in its endogenous context, and they found that Gal4 cluster formation is facilitated by, but does not completely depend on DNA binding and intrinsically disordered regions.
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Analysis of genomic loci harboring 59,732 human-specific regulatory sequences reveals unique to human regulatory patterns associated with brain development
TL;DR: A comprehensive catalogue of 59,732 genomic loci harboring candidate human-specific regulatory sequences (HSRS) has been assembled to facilitate the systematic analyses of genomic sequences that were either inherited from extinct common ancestors (ECAs) or created de novo in human genomes as discussed by the authors.
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