ArticlePloS one2009
Polycomb mediated epigenetic silencing and replication timing at the INK4a/ARF locus during senescence.
Article in PloS one, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 1 of them a synthesis that pooled it.
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Who cites it
76 citing papers in PubMed, 1 synthesis or guideline pooled it, 132 citations in OpenAlex.
- Genotranscriptomic meta-analysis of the Polycomb gene CBX2 in human cancers: initial evidence of an oncogenic role.British journal of cancer · 2014Pooled it
- EZH2 promotes malignant phenotypes and is a predictor of oral cancer development in patients with oral leukoplakia.Cancer prevention research (Philadelphia, Pa.) · 2011Trial
- CDC6 promotes the development and progression of clear cell renal cell carcinoma via upregulating RRM2.Human cell · 2025Article
- Mineral Stress Drives Loss of Heterochromatin: An Early Harbinger of Vascular Inflammaging and Calcification.Circulation research · 2025Article
- A scoping review regarding reproductive capacity modulation based on alpha-ketoglutarate supplementation.Reproduction (Cambridge, England) · 2024Article
- Biomarkers of aging.Science China. Life sciences · 2023Review
- Review
- CircularRNA biology · 2021Article
- Epigenetic regulation of satellite cell fate during skeletal muscle regeneration.Skeletal muscle · 2021Review
- The Pivotal Immunomodulatory and Anti-Inflammatory Effect of Histone-Lysine N-Methyltransferase in the Glioma Microenvironment: Its Biomarker and Therapy Potentials.Analytical cellular pathology (Amsterdam) · 2021Review
- Genetic and Epigenetic Characterization of Pulpal and Periapical Inflammation.Frontiers in physiology · 2020Review
- JMJD3 in the regulation of human diseases.Protein & cell · 2019Review
- Jumonji C Demethylases in Cellular Senescence.Genes · 2019Review
- Aberrant expression of p16Cancer reports and reviews · 2018Article
- Jun dimerization protein 2 controls hypoxia-induced replicative senescence via both the p16FEBS open bio · 2017Article
- Regulation of the JMJD3 (KDM6B) histone demethylase in glioblastoma stem cells by STAT3.PloS one · 2017Article
- MSK1 triggers the expression of the INK4AB/ARF locus in oncogene-induced senescence.Molecular biology of the cell · 2016Article
- Islet biology, the CDKN2A/B locus and type 2 diabetes risk.Diabetologia · 2016Review
- Nuclear receptor NR5A2 controls neural stem cell fate decisions during development.Nature communications · 2016Article
- EZH2 promotes metabolic reprogramming in glioblastomas through epigenetic repression of EAF2-HIF1α signaling.Oncotarget · 2016Article
16 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe INK4/ARF locus encodes three tumor suppressor genes (p15(Ink4b), Arf and p16(Ink4a)) and is frequently inactivated in a large number of human cancers. Mechanisms regulating INK4/ARF expression are not fully characterized. PRINCIPAL
findingsHere we show that in young proliferating embryonic fibroblasts (MEFs) the Polycomb Repressive Complex 2 (PRC2) member EZH2 together with PRC1 members BMI1 and M33 are strongly expressed and localized at the INK4/ARF regulatory domain (RD) identified as a DNA replication origin. When cells enter senescence the binding to RD of both PRC1 and PRC2 complexes is lost leading to a decreased level of histone H3K27 trimethylation (H3K27me3). This loss is accompanied with an increased expression of the histone demethylase Jmjd3 and with the recruitment of the MLL1 protein, and correlates with the expression of the Ink4a/Arf genes. Moreover, we show that the Polycomb protein BMI1 interacts with CDC6, an essential regulator of DNA replication in eukaryotic cells. Finally, we demonstrate that Polycomb proteins and associated epigenetic marks are crucial for the control of the replication timing of the INK4a/ARF locus during senescence.
conclusionsWe identified the replication licencing factor CDC6 as a new partner of the Polycomb group member BMI1. Our results suggest that in young cells Polycomb proteins are recruited to the INK4/ARF locus through CDC6 and the resulting silent locus is replicated during late S-phase. Upon senescence, Jmjd3 is overexpressed and the MLL1 protein is recruited to the locus provoking the dissociation of Polycomb from the INK4/ARF locus, its transcriptional activation and its replication during early S-phase. Together, these results provide a unified model that integrates replication, transcription and epigenetics at the INK4/ARF locus.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.