Molecular Interplay of the Noncoding RNA ANRIL and Methylated Histone H3 Lysine 27 by Polycomb CBX7 in Transcriptional Silencing of INK4a
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Expression of the INK4b/ARF/INK4a tumor suppressor locus in normal and cancerous cell growth is controlled by methylation of histone H3 at lysine 27 (H3K27me) as directed by the Polycomb group proteins. The antisense noncoding RNA ANRIL of the INK4b/ARF/INK4a locus is also important for expression of the protein-coding genes in cis, but its mechanism has remained elusive. Here we report that chromobox 7 (CBX7) within the polycomb repressive complex 1 binds to ANRIL, and both CBX7 and ANRIL are found at elevated levels in prostate cancer tissues. In concert with H3K27me recognition, binding to RNA contributes to CBX7 function, and disruption of either interaction impacts the ability of CBX7 to repress the INK4b/ARF/INK4a locus and control senescence. Structure-guided analysis reveals the molecular interplay between noncoding RNA and H3K27me as mediated by the conserved chromodomain. Our study suggests a mechanism by which noncoding RNA participates directly in epigenetic transcriptional repression.
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In proliferative cells, polycomb repressive complexes PRC1 and PRC2 are recruited by the long noncoding RNA ANRIL to the CDKN2A locus.
“In proliferative cells, polycomb repressive complexes (PRC1 and PRC2) are recruited by the long noncoding RNA ANRIL to the CDKN2A locus [79].”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [79]
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Rahnamoun, H., Orozco, P., & Lauberth, S. M. (2020) · Transcription · doi:10.1080/21541264.2019.1698934 · Cited by 16 · see citing works
- Authors
- Yap, K. L., Li, S., Muñoz-Cabello, A. M., Raguz, S., Zeng, L., Mujtaba, S., Gil, J., Walsh, M. J., & Zhou, M.-M.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- Imperial College London (GB)
- Corresponding author
- Walsh, Martin J.
- Zhou, Ming-Ming
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2010-06
- Volume
- 38
- Issue
- 5
- Pages
- 662-674
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC2886305
- OpenAlex
- W2052741109
- Cited by
- 1,391
- References
- 62
- Citations by year
- 2026: 27 · 2025: 43 · 2024: 44 · 2023: 54 · 2022: 61 · 2021: 86 · 2020: 78 · 2019: 94 · 2018: 112 · 2017: 113 · 2016: 120 · 2015: 129 · 2014: 122 · 2013: 116 · 2012: 104
- FWCI
- 40.29
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Drug Abuse (RC1DA028776)
- National Human Genome Research Institute (R01HG004508)
- National Cancer Institute (R01CA087658)
- National Institute of General Medical Sciences (R01GM073207)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- 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
- Keywords
- ANRIL, CBX7, PRC1, INK4A, transcriptional silencing, chromodomain, prostate cancer, cellular senescence
- MeSH terms
- Animals, Multigene Family, Histones, Humans, Lysine, Male, Methylation, Models, Molecular, Molecular Sequence Data, Prostatic Neoplasms, Repressor Proteins, Transcription, Genetic, Cellular Senescence, Protein Structure, Tertiary, Nuclear Magnetic Resonance, Biomolecular, Cyclin-Dependent Kinase Inhibitor p16, Gene Silencing, RNA, Untranslated, Cell Line, Tumor, Cyclin-Dependent Kinase Inhibitor p15, Polycomb-Group Proteins, Polycomb Repressive Complex 1
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