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Cited by 143Genomics and Chromatin DynamicsChromatin Remodeling and CancerCancer-related molecular mechanisms research

3D enhancer-promoter interactions and multi-connected hubs: Organizational principles and functional roles

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Uyehara, Christopher M., Apostolou, Effie·2023·Cell Reports
DOI 10.1016/j.celrep.2023.112068PMC PMC10556201
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Abstract

The spatiotemporal control of gene expression is dependent on the activity of cis-acting regulatory sequences, called enhancers, which regulate target genes over variable genomic distances and, often, by skipping intermediate promoters, suggesting mechanisms that control enhancer-promoter communication. Recent genomics and imaging technologies have revealed highly complex enhancer-promoter interaction networks, whereas advanced functional studies have started interrogating the forces behind the physical and functional communication among multiple enhancers and promoters. In this review, we first summarize our current understanding of the factors involved in enhancer-promoter communication, with a particular focus on recent papers that have revealed new layers of complexities to old questions. In the second part of the review, we focus on a subset of highly connected enhancer-promoter "hubs" and discuss their potential functions in signal integration and gene regulation, as well as the putative factors that might determine their dynamics and assembly.

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  • GPC3 overexpression in HCC is accompanied by significant 3D interactions among constituent enhancers and between constituent enhancers and the promoter.

    “GPC3 overexpression was accompanied by significant 3D interactions amongst constituent enhancers as well as between constituent enhancers and the promoter (Fig. 3b)66,67.”

    From Multi-omic analysis of hepatocellular carcinoma reveals aberrant cis-regulatory changes and dysregulated retrotransposons with prognostic potential (2025) · cites this paper as [67]

    The Introduction section on highly multi-connected 3D hubs discusses enhancer–promoter interactions generally and gives examples at other loci, including PVT1. Searches for GPC3, HCC, and hepatocellular carcinoma found no passage in our copy addressing GPC3 overexpression or the claimed interactions among its enhancers and promoter. (LLM, conf=0.76)

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Authors
Uyehara, C. M., & Apostolou, E.
Affiliations
Weill Cornell Medicine (US)
Corresponding author
Apostolou, Effie
ORCID
Venue
Cell Reports
Publisher
Elsevier BV
Published
2023-04
Volume
42
Issue
4
Pages
112068
ISSN
2211-1247 (ISSN-L)
DOI
10.1016/j.celrep.2023.112068
PMC
PMC10556201
OpenAlex
W4365445758
Cited by
143
References
159
Citations by year
2026: 40 · 2025: 42 · 2024: 44 · 2023: 17
FWCI
3.80
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Reports (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • NIGMS (R01GM138635, RM1GM139738)
  • NIDDK (U01DK128852)
  • New York State Department of Health
  • New York State Stem Cell Science
  • The Mark Foundation for Cancer Research
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
enhancer-promoter interactions, 3D genome organization, cis-regulatory elements, signal integration, gene expression regulation
MeSH terms
Enhancer Elements, Genetic, Gene Expression Regulation, Promoter Regions, Genetic, Genomics

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