Enhancer RNAs participate in androgen receptor-driven looping that selectively enhances gene activation
Open accessAbstract
Significance: We report that enhancer RNAs (eRNAs), a class of long noncoding RNAs, participate in the androgen receptor (AR)-dependent looping complex that enhances spatial communication of distal enhancers and target promoters, leading to transcriptional activation events. Furthermore, our data show that KLK3 eRNA (KLK3e) selectively enhances the gene expression of AR-regulated genes, and provide evidence for a positive regulatory loop in which AR-dependent transcription is modulated by an intermediate eRNA. These findings may translate into improved RNA-based therapy (eRNA suppression) to enhance the durability of androgen deprivation therapy (ADT) and prediction of the efficacy of ADT by measuring the enhancer-derived activity (eRNA expression) in prostate tumors.
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Knockdown of selected enhancer RNAs reduces expression of the corresponding gene targets, suggesting functionality.
“However, studies that knock down selected eRNA have found reduced expression of the corresponding gene targets, suggesting functionality [79–81].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [81]
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 [81]
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 [68]
Cites
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A Large Fraction of Extragenic RNA Pol II Transcription Sites Overlap Enhancers
De Santa, F., Barozzi, I., Mietton, F., Ghisletti, S., Polletti, S., Tusi, B. K., Muller, H., Ragoussis, J., Wei, C.-L., & Natoli, G. (2010) · PLoS Biology · doi:10.1371/journal.pbio.1000384 · Cited by 934 · see citing works
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RNA Binding to CBP Stimulates Histone Acetylation and Transcription
Bose, D. A., Donahue, G., Reinberg, D., Shiekhattar, R., Bonasio, R., & Berger, S. L. (2017) · Cell · doi:10.1016/j.cell.2016.12.020 · Cited by 426 · see citing works
Transcription in Living Cells: Molecular Mechanisms of Bursting
Rodriguez, J., & Larson, D. R. (2020) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-011520-105250 · Cited by 224 · see citing works
Histone Deacetylases Positively Regulate Transcription through the Elongation Machinery
Greer, C. B., Tanaka, Y., Kim, Y. J., Xie, P., Zhang, M. Q., Park, I.-H., & Kim, T. H. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.10.013 · Cited by 174 · see citing works
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Transcriptional enhancers and their communication with gene promoters
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Enhancer RNA: Biogenesis, function, and regulation
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Enhancer Function in the 3D Genome
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The role of enhancer RNAs in epigenetic regulation of gene expression
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- Authors
- Hsieh, C.-L., Fei, T., Chen, Y., Li, T., Gao, Y., Wang, X., Sun, T., Sweeney, C. J., Lee, G.-S. M., Chen, S., Balk, S. P., Liu, X. S., Brown, M., & Kantoff, P. W.
- Affiliations
- Harvard University (US)
- Beth Israel Deaconess Medical Center (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2014-04-28
- Volume
- 111
- Issue
- 20
- Pages
- 7319-7324
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4034202
- OpenAlex
- W1995226230
- Cited by
- 398
- References
- 2
- Citations by year
- 2026: 15 · 2025: 18 · 2024: 26 · 2023: 33 · 2022: 41 · 2021: 62 · 2020: 46 · 2019: 28 · 2018: 33 · 2017: 27 · 2016: 29 · 2015: 27 · 2014: 11
- FWCI
- 12.86
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- Funders
- National Cancer Institute (P50CA090381, K99CA175290, P01CA163227)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Keywords
- enhancer RNA, androgen receptor, enhancer-promoter looping, prostate-specific antigen, KLK2, MED1, chromatin structure, prostate cancer, gene expression regulation
- MeSH terms
- Animals, Chlorocebus aethiops, Enhancer Elements, Genetic, Humans, Kallikreins, Male, Promoter Regions, Genetic, Prostate, Prostatic Neoplasms, Receptors, Androgen, Regulatory Sequences, Nucleic Acid, Transcription, Genetic, Transcriptional Activation, Gene Expression Regulation, Neoplastic, Prostate-Specific Antigen, COS Cells, Tissue Kallikreins, Gene Silencing, RNA Interference, Cell Line, Tumor, Mediator Complex Subunit 1
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