Cited by 1,753Genomics and Chromatin DynamicsGene Regulatory Network AnalysisChromatin Remodeling and Cancer

A Phase Separation Model for Transcriptional Control

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Hnisz, Denes, Shrinivas, Krishna, Young, Richard A., Chakraborty, Arup K., Sharp, Phillip A.·2017·Cell

Abstract

Phase-separated multi-molecular assemblies provide a general regulatory mechanism to compartmentalize biochemical reactions within cells. We propose that a phase separation model explains established and recently described features of transcriptional control. These features include the formation of super-enhancers, the sensitivity of super-enhancers to perturbation, the transcriptional bursting patterns of enhancers, and the ability of an enhancer to produce simultaneous activation at multiple genes. This model provides a conceptual framework to further explore principles of gene control in mammals.

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Crossref · 10.1016/j.cell.2017.02.007

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  • Current results strongly suggest that the demixing of enhancer- and promoter-associated proteins results in the assembly of a phase condensate that keeps the enhancer and promoter in spatial proximity.

    “Current results strongly suggest that the demixing of enhancer- and promoter-associated proteins results in the assembly of a phase condensate that keeps the enhancer and promoter in spatial proximity [97,98,99].”

    From Enhancer Function in the 3D Genome (2023) · cites this paper as [98]

    In “Formation of membraneless organelles by phase separation” (page unavailable), the paper hypothesizes that a phase-separated assembly forms at super-enhancers. In “A phase separation model of enhancer assembly and function” (page unavailable), it proposes that the assembly includes factors bound at both enhancers and promoters. It does not establish that such a condensate forms in vivo or keeps enhancers and promoters in spatial proximity, so the claim presents the proposed mechanism more strongly than the source does. (LLM, conf=0.84)

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Cited by

Sorted by citations

Authors
Hnisz, D., Shrinivas, K., Young, R. A., Chakraborty, A. K., & Sharp, P. A.
Affiliations
  • Whitehead Institute for Biomedical Research (US)
  • Harvard University (US)
  • Koch Institute for Integrative Cancer Research At MIT (US)
Corresponding author
  • Young, Richard A.
  • Chakraborty, Arup K.
  • Sharp, Phillip A.
Venue
Cell
Publisher
Elsevier BV
Published
2017-03
Volume
169
Issue
1
Pages
13-23
ISSN
0092-8674 (ISSN-L)
OpenAlex
W2603000633
Cited by
1,753
References
11
Citations by year
2026: 133 · 2025: 186 · 2024: 197 · 2023: 184 · 2022: 205 · 2021: 276 · 2020: 218 · 2019: 175 · 2018: 144 · 2017: 34
FWCI
14.62
Type
journal article
Language
en
Open access
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-nd)
  • PMC
Funders
  • National Cancer Institute
  • Austrian Science Fund (P01-CA042063, P30-CA14051)
  • National Institutes of Health (HG002668, J3490)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
Keywords
phase separation, transcriptional regulation, super-enhancers, enhancers, transcriptional bursting, gene expression regulation, liquid-liquid phase separation, enhancer activation
MeSH terms
Animals, Enhancer Elements, Genetic, Eukaryotic Cells, Gene Expression Regulation, Humans, Models, Biological, Transcription Factors, Transcription, Genetic, Transcriptional Activation

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