ArticleGenome biology2016
Mapping H4K20me3 onto the chromatin landscape of senescent cells indicates a function in control of cell senescence and tumor suppression through preservation of genetic and epigenetic stability.
Article in Genome biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers, 2 of them syntheses that pooled it.
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Who cites it
71 citing papers in PubMed, 2 syntheses or guidelines pooled it, 102 citations in OpenAlex.
- Cellular Senescence and Immunosenescence in Melanoma: Insights From the Tumor Microenvironment.Cancer medicine · 2025Pooled it
- Broad repression of DNA repair genes in senescent cells identified by integration of transcriptomic data.Nucleic acids research · 2025Pooled it
- H4K20me3 erasure facilitates reprogramming to totipotent-like state by promotingFundamental research · 2026Article
- Host-Pathogen Interaction as a Driver of Cellular Senescence: Microbial Triggers and Host Response.International journal of molecular sciences · 2026Review
- The sleeping threat: targeting cancer dormancy to transform metastasis therapy.Nature reviews. Cancer · 2026Review
- Expression profiles of histone H4K20 methylation and its associated enzymes in mouse cardiac disease and human heart failure.Epigenetics · 2025Article
- Oncogenic and immunomodulatory functions of SUV420H1 in HPV-negative head and neck squamous cell carcinoma.bioRxiv : the preprint server for biology · 2025Article
- Interrogating the regulatory epigenome of cellular senescence.Cellular and molecular life sciences : CMLS · 2025Review
- A transcriptome-based human universal senescence index (hUSI) robustly predicts cellular senescence under various conditions.Nature aging · 2025Article
- Assessing Large Multimodal Models for One-Shot Learning and Interpretability in Biomedical Image Classification.Advanced intelligent systems (Weinheim an der Bergstrasse, Germany) · 2025Article
- A narrative review of epigenetic marker in H3K27ac and its emerging potential as a therapeutic target in cancer.Epigenomics · 2025Review
- In Situ and In Silico Methods for Senescence Identification in Human Liver Diseases.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Remodeling of cytoskeleton, chromatin, and gene expression during mechanical rejuvenation of aged human dermal fibroblasts.Molecular biology of the cell · 2025Article
- Interplay between epigenetics, senescence and cellular redox metabolism in cancer and its therapeutic implications.Redox biology · 2024Review
- Epigenetic Regulation by Histone Methylation and Demethylation in Freeze-Tolerant Frog Kidney.Cell biochemistry and function · 2024Article
- Emerging insights in senescence: pathways from preclinical models to therapeutic innovations.npj aging · 2024Review
- Repressor elements provide insights into tissue development and phenotypes in pigs.Zoological research · 2024Article
- The impact of cell states on heterochromatin dynamics.The Biochemical journal · 2024Review
- Histone H4 acetylation differentially modulates proliferation in adult oligodendrocyte progenitors.The Journal of cell biology · 2024Article
- The role of the dynamic epigenetic landscape in senescence: orchestrating SASP expression.npj aging · 2024Review
11 more citing papers are in PubMed but not listed here.
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Authors and funding
23 authors at 9 institutions in 3 countries.
Funding
Abstract
backgroundHistone modification H4K20me3 and its methyltransferase SUV420H2 have been implicated in suppression of tumorigenesis. The underlying mechanism is unclear, although H4K20me3 abundance increases during cellular senescence, a stable proliferation arrest and tumor suppressor process, triggered by diverse molecular cues, including activated oncogenes. Here, we investigate the function of H4K20me3 in senescence and tumor suppression.
resultsUsing immunofluorescence and ChIP-seq we determine the distribution of H4K20me3 in proliferating and senescent human cells. Altered H4K20me3 in senescence is coupled to H4K16ac and DNA methylation changes in senescence. In senescent cells, H4K20me3 is especially enriched at DNA sequences contained within specialized domains of senescence-associated heterochromatin foci (SAHF), as well as specific families of non-genic and genic repeats. Altered H4K20me3 does not correlate strongly with changes in gene expression between proliferating and senescent cells; however, in senescent cells, but not proliferating cells, H4K20me3 enrichment at gene bodies correlates inversely with gene expression, reflecting de novo accumulation of H4K20me3 at repressed genes in senescent cells, including at genes also repressed in proliferating cells. Although elevated SUV420H2 upregulates H4K20me3, this does not accelerate senescence of primary human cells. However, elevated SUV420H2/H4K20me3 reinforces oncogene-induced senescence-associated proliferation arrest and slows tumorigenesis in vivo.
conclusionsThese results corroborate a role for chromatin in underpinning the senescence phenotype but do not support a major role for H4K20me3 in initiation of senescence. Rather, we speculate that H4K20me3 plays a role in heterochromatinization and stabilization of the epigenome and genome of pre-malignant, oncogene-expressing senescent cells, thereby suppressing epigenetic and genetic instability and contributing to long-term senescence-mediated tumor suppression.
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Registered trials
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.