Mediator and RNA polymerase II clusters associate in transcription-dependent condensates

American Association for the Advancement of Science (AAAS) - Tập 361 Số 6400 - Trang 412-415 - 2018
Won‐Ki Cho1, Jan-Hendrik Spille1, Micca Hecht1, Choongman Lee1, Charles Li2,3, Valentin Grube4,1, I. Cissé1
1Department of Physics, MIT, Cambridge, MA 02139, USA
2Department of Biology, MIT, Cambridge, MA 02139, USA
3Whitehead Institute for Biomedical Research, Cambridge, MA 02139, USA
4Department of Physics, LMU Munich, Geschwister Scholl Platz 1, 80539 Munich, Germany

Tóm tắt

Phase separation and gene control Many components of eukaryotic transcription machinery—such as transcription factors and cofactors including BRD4, subunits of the Mediator complex, and RNA polymerase II—contain intrinsically disordered low-complexity domains. Now a conceptual framework connecting the nature and behavior of their interactions to their functions in transcription regulation is emerging (see the Perspective by Plys and Kingston). Chong et al. found that low-complexity domains of transcription factors form concentrated hubs via functionally relevant dynamic, multivalent, and sequence-specific protein-protein interaction. These hubs have the potential to phase-separate at higher concentrations. Indeed, Sabari et al. showed that at super-enhancers, BRD4 and Mediator form liquid-like condensates that compartmentalize and concentrate the transcription apparatus to maintain expression of key cell-identity genes. Cho et al. further revealed the differential sensitivity of Mediator and RNA polymerase II condensates to selective transcription inhibitors and how their dynamic interactions might initiate transcription elongation. Science , this issue p. eaar2555 , p. eaar3958 , p. 412 ; see also p. 329

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American Association for the Advancement of Science (AAAS)

Tập 361 Số 6400

412-415

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