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Cited by 1,049Cancer-related molecular mechanisms researchGenomics and Chromatin DynamicsEstrogen and related hormone effects

Functional roles of enhancer RNAs for oestrogen-dependent transcriptional activation

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Li, Wenbo, Notani, Dimple, Ma, Qi, Tanasa, Bogdan, Nunez, Esperanza, Chen, Aaron Yun, Merkurjev, Daria, Zhang, Jie +6 more·2013·Nature
DOI 10.1038/nature12210PMC PMC3718886
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Abstract

The functional importance of gene enhancers in regulated gene expression is well established. In addition to widespread transcription of long non-coding RNAs (lncRNAs) in mammalian cells, bidirectional ncRNAs are transcribed on enhancers, and are thus referred to as enhancer RNAs (eRNAs). However, it has remained unclear whether these eRNAs are functional or merely a reflection of enhancer activation. Here we report that in human breast cancer cells 17β-oestradiol (E2)-bound oestrogen receptor α (ER-α) causes a global increase in eRNA transcription on enhancers adjacent to E2-upregulated coding genes. These induced eRNAs, as functional transcripts, seem to exert important roles for the observed ligand-dependent induction of target coding genes, increasing the strength of specific enhancer-promoter looping initiated by ER-α binding. Cohesin, present on many ER-α-regulated enhancers even before ligand treatment, apparently contributes to E2-dependent gene activation, at least in part by stabilizing E2/ER-α/eRNA-induced enhancer-promoter looping. Our data indicate that eRNAs are likely to have important functions in many regulated programs of gene transcription.

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  • Knockdown of eRNAs resulted in decreased enhancer-promoter proximity in human cells.

    “Knockdown of eRNAs resulted in decreased enhancer–promoter proximity in human cells [81, 390].”

    From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [390]

  • The results of several studies suggest the involvement of eRNA in the formation of enhancer-promoter loops.

    “The results of several studies suggest the involvement of eRNA in the formation of enhancer-promoter loops, although the specific mechanisms remain unclear [68,69].”

    From Enhancer Function in the 3D Genome (2023) · cites this paper as [69]

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Research works printed but not linked: 34

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Authors
Li, W., Notani, D., Ma, Q., Tanasa, B., Nunez, E., Chen, A. Y., Merkurjev, D., Zhang, J., Ohgi, K., Song, X., Oh, S., Kim, H.-S., Glass, C. K., & Rosenfeld, M. G.
Affiliations
  • Howard Hughes Medical Institute (US)
  • University of California San Diego (US)
Corresponding author
Rosenfeld, Michael G.
ORCID
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2013-06
Volume
498
Issue
7455
Pages
516-520
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/nature12210
PMC
PMC3718886
OpenAlex
W2111099379
Cited by
1,049
References
6
Citations by year
2026: 33 · 2025: 60 · 2024: 74 · 2023: 67 · 2022: 79 · 2021: 106 · 2020: 70 · 2019: 81 · 2018: 76 · 2017: 84 · 2016: 92 · 2015: 97 · 2014: 88 · 2013: 41
FWCI
37.30
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
Funders
  • U.S. Department of Defense
  • Howard Hughes Medical Institute
  • University of California, San Diego
  • National Heart, Lung, and Blood Institute (R01HL065445, HL065445)
  • National Cancer Institute (P30-CA-23100, R01CA097134, CA173903, R01CA173903, P30CA023100, T32CA009523)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK039949, DK 039949, DK018477, R37DK039949, R01DK018477)
  • National Institute of Neurological Disorders and Stroke (R01NS034934, NS034934)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
Keywords
enhancer RNA, long non-coding RNA, estrogen receptor alpha, enhancer-promoter looping, cohesin, breast cancer cells, estradiol, nuclear receptors, REV-ERB, enhancer function, gene expression regulation
MeSH terms
Cohesins, Chromosomal Proteins, Non-Histone, Enhancer Elements, Genetic, Estradiol, Estrogens, Humans, Ligands, Nucleic Acid Conformation, Promoter Regions, Genetic, Transcription, Genetic, Transcriptional Activation, Cell Cycle Proteins, RNA, Untranslated, Estrogen Receptor alpha, MCF-7 Cells

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