Enhancers as non-coding RNA transcription units: recent insights and future perspectives
Abstract
Networks of regulatory enhancers dictate distinct cell identities and cellular responses to diverse signals by instructing precise spatiotemporal patterns of gene expression. However, 35 years after their discovery, enhancer functions and mechanisms remain incompletely understood. Intriguingly, recent evidence suggests that many, if not all, functional enhancers are themselves transcription units, generating non-coding enhancer RNAs. This observation provides a fundamental insight into the inter-regulation between enhancers and promoters, which can both act as transcription units; it also raises crucial questions regarding the potential biological roles of the enhancer transcription process and non-coding enhancer RNAs. Here, we review research progress in this field and discuss several important, unresolved questions regarding the roles and mechanisms of enhancers in gene regulation.
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Total RNA-seq can detect more eRNAs than polyA RNA-seq because not all eRNAs are polyadenylated.
“Given that not all eRNAs are polyadenylated, total RNA-seq, compared to polyA RNA-seq, can detect more eRNAs (78, 79).”
From Comprehensive characterization of the transcriptional landscape in Alzheimer’s disease (AD) brains (2025) · cites this paper as [78]
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“Therefore, some eRNAs may be functional entities while others simply have transcription-dependent functions, meaning that the act of transcribing the eRNA itself may be important for subsequent downstream activities such as transcription factor (TF) binding (20, 51).”
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“Given that not all eRNAs are polyadenylated, total RNA-seq, compared to polyA RNA-seq, can detect more eRNAs ( 78 , 79 ).”
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- Authors
- Li, W., Notani, D., & Rosenfeld, M. G.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Rosenfeld, Michael G.
- Venue
- Nature Reviews Genetics
- Published
- 2016-03-07
- Volume
- 17
- Issue
- 4
- Pages
- 207-223
- ISSN
- 1471-0056 (ISSN-L)
- 1471-0064
- OpenAlex
- W2295037017
- Cited by
- 710
- References
- 22
- Citations by year
- 2026: 24 · 2025: 39 · 2024: 50 · 2023: 56 · 2022: 81 · 2021: 92 · 2020: 83 · 2019: 86 · 2018: 87 · 2017: 88 · 2016: 24
- FWCI
- 8.61
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Genetics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Defense
- Howard Hughes Medical Institute
- National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Keywords
- enhancers, enhancer transcription, enhancer-promoter interactions, gene expression regulation, transcriptional regulation, cell identity, spatiotemporal gene expression, regulatory networks
- MeSH terms
- Animals, Enhancer Elements, Genetic, Gene Expression Regulation, Multigene Family, Humans, Models, Genetic, Promoter Regions, Genetic, RNA Processing, Post-Transcriptional, Transcription Factors, Transcription, Genetic, RNA, Untranslated, Genomic Instability
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