Cited by 202Epigenetics and DNA MethylationChromatin Remodeling and CancerGenomics and Chromatin Dynamics

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Epigenetic regulation of the INK4b-ARF-INK4a locus: In sickness and in health

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Popov, Nikolay, Gil, Jesús·2010·Epigenetics

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Abstract

The INK4b-ARF-INK4a locus encodes for two cyclin-dependent kinase inhibitors, p15(INK4b) and p16(INK4a) and a regulator of the p53 pathway, ARF. In addition ANRIL, a non-coding RNA, is also transcribed from the locus. ARF, p15(INK4b) and p16(INK4a) are well-established tumor suppressors which function is frequently disabled in human cancers. Recent studies showed that single nucleotide polymorphisms mapping in the vicinity of ANRIL are linked to a wide spectrum of conditions, including cardiovascular disease, ischemic stroke, type 2 diabetes, frailty and Alzheimer's disease. The INK4b-ARF-INK4a locus is regulated by Polycomb repressive complexes (PRCs), and its expression can be invoked by activating signals. Other epigenetic modifiers such as the histone demethylases JMJD3 and JHDM1B, the SWI/SNF chromatin remodeling complex and DNA methyltransferases regulate the locus interplaying with PRCs. In view of the intimate involvement of the INK4b-ARF-INK4a locus on disease, to understand its regulation is the first step for manipulate it to therapeutic benefit.

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Authors: Popov, N., & Gil, J.
Affiliations: Imperial College London (GB)
Corresponding author: Gil, Jesús
ORCID: Gil, Jesús
Venue: Epigenetics
Publisher: Informa UK Limited
Published: 2010-11
Volume: 5
Issue: 8
Pages: 685-690
ISSN: 1559-2294 (ISSN-L)
1559-2308
DOI: 10.4161/epi.5.8.12996
PMC: PMC3052884
OpenAlex: W1969204301
Cited by: 202
References: 72
Citations by year: 2026: 2 · 2025: 5 · 2024: 3 · 2023: 4 · 2022: 8 · 2021: 9 · 2020: 15 · 2019: 14 · 2018: 14 · 2017: 16 · 2016: 13 · 2015: 24 · 2014: 21 · 2013: 26 · 2012: 18
FWCI: 1.51
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Epigenetics (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: LifeArc
Cancer Research UK
Medical Research Council
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords: p16INK4a, CDKN2B, ARF, ANRIL, non-coding RNA, polycomb repressive complex, histone demethylase, JMJD3, SWI/SNF chromatin remodeling, DNA methyltransferases, tumor suppressor, single nucleotide polymorphisms, epigenetic regulation, cancer
MeSH terms: Alzheimer Disease, Animals, Cardiovascular Diseases, Chromatin, Diabetes Mellitus, Type 2, Humans, Repressor Proteins, Transcription, Genetic, DNA Modification Methylases, Signal Transduction, Tumor Suppressor Protein p53, G1 Phase, Cyclin-Dependent Kinase Inhibitor p16, ADP-Ribosylation Factors, RNA, Untranslated, Epigenesis, Genetic, Cyclin-Dependent Kinase Inhibitor p15, Cyclin-Dependent Kinase 4, Cyclin-Dependent Kinase 6, Proto-Oncogene Proteins c-mdm2, Genetic Loci, Histone Demethylases, Polycomb-Group Proteins

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Epigenetic regulation of the INK4b-ARF-INK4a locus: In sickness and in health

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