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Cited by 966Genomics and Chromatin DynamicsRNA Research and SplicingProtein Structure and Dynamics

Imaging dynamic and selective low-complexity domain interactions that control gene transcription

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Chong, Shasha, Dugast-Darzacq, Claire, Liu, Zhe, Dong, Peng, Dailey, Gina M., Cattoglio, Claudia, Heckert, Alec, Banala, Sambashiva +3 more·2018·Science
DOI 10.1126/science.aar2555PMC PMC6961784
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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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  • High-concentration hubs were capable of transactivation and recruitment of RNAP even without LLPS.

    “Furthermore, since high-concentration hubs were capable of transactivation and recruitment of RNAP even without LLPS, the question remains if LLPS is necessary for any genomic locus [412].”

    From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [412]

    The ‘LCD hubs interact with RNA Pol II’ section reports polymerase enrichment in LCD hubs, and the Discussion reports transactivation at native chromosomal loci without detectable phase separation. The paper says phase separation was not detected at endogenous expression levels; it does not establish that LLPS was absent, as the claim’s unqualified wording implies. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • TFs were shown to form high-concentration stochastic hubs with chromatin in living human cells, and overexpression of their low complexity domains beyond endogenous levels was required for LLPS to occur.

    “For instance, whilst TFs were shown to form high-concentration stochastic hubs with chromatin in living human cells, overexpression of their low complexity domains beyond endogenous levels was required for LLPS to occur [412].”

    From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [412]

    The Results and Discussion report dynamic, high-concentration TF LCD hubs at endogenous genomic loci in live cells. The Discussion says apparent liquid–liquid phase separation was detected with gross LCD overexpression, but not detected in hubs at endogenous expression levels. That observation does not establish that overexpression is required for phase separation to occur. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

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Authors
Chong, S., Dugast-Darzacq, C., Liu, Z., Dong, P., Dailey, G. M., Cattoglio, C., Heckert, A., Banala, S., Lavis, L., Darzacq, X., & Tjian, R.
Affiliations
  • Howard Hughes Medical Institute (US)
  • Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA.
  • University of California, Berkeley (US)
Corresponding author
Tjian, Robert
ORCID
Venue
Science
Publisher
American Association for the Advancement of Science (AAAS)
Published
2018-07-27
Volume
361
Issue
6400
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
DOI
10.1126/science.aar2555
PMC
PMC6961784
OpenAlex
W2808847099
Cited by
966
References
4
Citations by year
2026: 70 · 2025: 93 · 2024: 112 · 2023: 123 · 2022: 143 · 2021: 175 · 2020: 117 · 2019: 94 · 2018: 36 · 2017: 1 · 2013: 1
FWCI
37.62
Type
journal article
Language
en
Open access
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • CaltechAUTHORS (California Institute of Technology) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • National Institutes of Health (UO1-EB021236 and U54-DK107980)
  • Howard Hughes Medical Institute
  • California Institute of Regenerative Medicine (LA1-08013)
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 › Protein Structure and Dynamics
Keywords
low-complexity domains, intrinsically disordered proteins, phase separation, liquid-like condensates, transcriptional regulation, BRD4, Mediator complex, RNA polymerase II, super-enhancers, protein-protein interaction, transcription elongation, transcription inhibitors, cell identity genes
MeSH terms
Single Molecule Imaging, DNA-Binding Proteins, Genes, Synthetic, Humans, Operator Regions, Genetic, Protein Binding, RNA Polymerase II, Transcription Factors, Transcription, Genetic, Transcriptional Activation, Cell Line, Tumor, Protein Interaction Domains and Motifs

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