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Cited by 1,403Genomics and Chromatin DynamicsRNA Research and SplicingChromatin Remodeling and Cancer

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

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Cho, Won-Ki, Spille, Jan-Hendrik, Hecht, Micca, Lee, Choongman, Li, Charles, Grube, Valentin, Cisse, Ibrahim I.·2018·Science
DOI 10.1126/science.aar4199PMC PMC6543815
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Abstract

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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  • Regulatory processes at the interface between enhancers and promoters have been estimated to occur in the order of tens of seconds.

    “Regulatory processes at the interface between enhancers and promoters have been estimated to occur in the order of tens of seconds41,43,46, consistent with the condition that intermediate regulatory steps should be faster than bursting kinetics (Fig. 3f).”

    From Nonlinear control of transcription through enhancer–promoter interactions (2022) · cites this paper as [43]

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Sorted by citations

Authors
Cho, W.-K., Spille, J.-H., Hecht, M., Lee, C., Li, C., Grube, V., & Cisse, I. I.
Affiliations
  • Massachusetts Institute of Technology (US)
  • Whitehead Institute for Biomedical Research (US)
  • Department of Physics, MIT, Cambridge, MA 02139, USA.
Corresponding author
  • Cho, Won-Ki
  • Spille, Jan-Hendrik
ORCID
Venue
Science
Publisher
American Association for the Advancement of Science (AAAS)
Published
2018-07-27
Volume
361
Issue
6400
Pages
412-415
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
DOI
10.1126/science.aar4199
PMC
PMC6543815
OpenAlex
W2809265915
Cited by
1,403
References
3
Citations by year
2026: 136 · 2025: 178 · 2024: 163 · 2023: 182 · 2022: 169 · 2021: 233 · 2020: 173 · 2019: 126 · 2018: 39 · 2017: 1
FWCI
51.59
Type
journal article
Language
en
Open access
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • CaltechAUTHORS (California Institute of Technology) (submittedVersion)
  • DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
  • MPG.PuRe (Max Planck Society) (submittedVersion)
Funders
  • NIH Office of the Director (#DP2CA195769)
  • Pew Charitable Trusts (Biomedical Scholars grant)
  • German Research Foundation (SP1680/1-1)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
Keywords
phase separation, liquid-like condensates, Mediator complex, RNA polymerase II, BRD4, low-complexity domains, intrinsically disordered proteins, super-enhancers, transcriptional regulation, transcription elongation, protein-protein interaction, transcription inhibitors, cell identity genes
MeSH terms
Animals, Cells, Cultured, Chromatin, Enhancer Elements, Genetic, Gene Expression Regulation, Luminescent Proteins, RNA Polymerase II, Transcription Factors, Transcription, Genetic, Mice, Embryonic Stem Cells, Mediator Complex, Molecular Imaging

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