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Cited by 154Genomics and Chromatin DynamicsChromatin Remodeling and CancerCancer-related molecular mechanisms research

Super-enhancers in transcriptional regulation and genome organization

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Wang, Xi, Cairns, Murray J, Yan, Jian·2019·Nucleic Acids Research
DOI 10.1093/nar/gkz1038PMC PMC7145697
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Abstract

Gene expression is precisely controlled in a stage and cell-type-specific manner, largely through the interaction between cis-regulatory elements and their associated trans-acting factors. Where these components aggregate in promoters and enhancers, they are able to cooperate to modulate chromatin structure and support the engagement in long-range 3D superstructures that shape the dynamics of a cell's genomic architecture. Recently, the term ‘super-enhancer’ has been introduced to describe a hyper-active regulatory domain comprising a complex array of sequence elements that work together to control the key gene networks involved in cell identity. Here, we survey the unique characteristics of super-enhancers compared to other enhancer types and summarize the recent advances in our understanding of their biological role in gene regulation. In particular, we discuss their capacity to attract the formation of phase-separated condensates, and capacity to generate three-dimensional genome structures that precisely activate their target genes. We also propose a multi-stage transition model to explain the evolutionary pressure driving the development of super-enhancers in complex organisms, and highlight the potential for involvement in tumorigenesis. Finally, we discuss more broadly the role of super-enhancers in human health disorders and related potential in therapeutic interventions.

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Cited by

Sorted by citations

Authors
Wang, X., Cairns, M. J., & Yan, J.
Affiliations
  • German Cancer Research Center (DE)
  • Hunter Medical Research Institute (AU)
  • City University of Hong Kong (HK)
Corresponding author
  • Wang, Xi
  • Yan, Jian
ORCID
Venue
Nucleic Acids Research
Publisher
Oxford University Press (OUP)
Published
2019-11-14
Volume
47
Issue
22
Pages
11481-11496
ISSN
  • 0305-1048 (ISSN-L)
  • 1362-4962
DOI
10.1093/nar/gkz1038
PMC
PMC7145697
OpenAlex
W2987062778
Cited by
154
References
18
Citations by year
2026: 11 · 2025: 24 · 2024: 22 · 2023: 20 · 2022: 30 · 2021: 26 · 2020: 19 · 2019: 2
FWCI
6.54
Type
journal article
Language
en
Open access
Licence
Locations
  • Nucleic Acids Research (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • CityU Scholars (submittedVersion, cc-by)
  • Figshare (submittedVersion, cc-by)
  • NOVA (University of Newcastle Australia) (submittedVersion, cc-by)
Funders
  • National Natural Science Foundation of China (81873642)
  • City University of Hong Kong (7200595, 7005314, 9667188, 9610424)
  • Ministry of Education
  • NHMRC (1121474)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
Keywords
super-enhancers, enhancers, transcriptional regulation, cis-regulatory elements, trans-acting factors, chromatin structure, 3D genome organization, phase-separated condensates, cell identity, carcinogenesis, gene expression regulation, therapeutic target
MeSH terms
Chromatin, Enhancer Elements, Genetic, Gene Expression Regulation, Humans, Neoplasms, Promoter Regions, Genetic, Gene Expression, Genome, Human, Cell Line, Tumor, Carcinogenesis

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