ArticleNucleic acids research2017
Accumulation of histone variant H3.3 with age is associated with profound changes in the histone methylation landscape.
Article in Nucleic acids research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers, 2 of them syntheses that pooled it.
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Who cites it
75 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Contribution of histone variants to aneuploidy: a cancer perspective.Frontiers in genetics · 2023Pooled it
- Pooled it
- Review
- Systemic epigenetic dysregulation as a driver of ageing and a therapeutic target.Nature reviews. Molecular cell biology · 2026Review
- Review
- HIRA-mediated H3.3 deposition preserves hepatocyte cell identity during liver aging.Research square · 2026Article
- Histone variant H2A.Z mutant suppresses the senescence-associated secretory phenotype.bioRxiv : the preprint server for biology · 2026Article
- A Proteoform-Resolved Atlas of Human Cardiac Histones.Research square · 2026Article
- Regulated cell death environments drive fibroinflammatory reprogramming in surviving adipose-derived stem cells.Apoptosis : an international journal on programmed cell death · 2025Article
- PBAF/cBAF reorganization on H3.3 chromatin regulates BMAL1 activity in the absence of circadian negative feedback.Nature communications · 2025Article
- Phosphorylation-mimicking histone H3.3 rescues exercise-induced gene responses in an epigenetic aging model of mouse skeletal muscle.Laboratory animal research · 2025Article
- Senescence-associated alterations in histone H3 modifications, HP1 alpha levels and distribution, and in the transcriptome of vascular smooth muscle cells in different types of senescence.Cell communication and signaling : CCS · 2025Article
- Exogenous expression of a histone H3.3 isoform causes extranuclear divisions in thebioRxiv : the preprint server for biology · 2025Article
- Normalized and Directional Interplay Scoring for the Interrogation of Proteoform Data.Journal of proteome research · 2025Article
- The role of the dynamic epigenetic landscape in senescence: orchestrating SASP expression.npj aging · 2024Review
- Age-related histone H3.3 accumulation associates with a repressive chromatin in mouse tibialis anterior muscle.The journal of physiological sciences : JPS · 2024Article
- asteRIa enables robust interaction modeling between chromatin modifications and epigenetic readers.Nucleic acids research · 2024Article
- Beyond the Usual Suspects: Examining the Role of Understudied Histone Variants in Breast Cancer.International journal of molecular sciences · 2024Review
- Plasma cell differentiation is regulated by the expression of histone variant H3.3.Nature communications · 2024Article
- Article
15 more citing papers are in PubMed but not listed here.
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5 authors.
Funding
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Abstract
Deposition of replication-independent histone variant H3.3 into chromatin is essential for many biological processes, including development and reproduction. Unlike replication-dependent H3.1/2 isoforms, H3.3 is expressed throughout the cell cycle and becomes enriched in postmitotic cells with age. However, lifelong dynamics of H3 variant replacement and the impact of this process on chromatin organization remain largely undefined. Using quantitative middle-down proteomics we demonstrate that H3.3 accumulates to near saturation levels in the chromatin of various mouse somatic tissues by late adulthood. Accumulation of H3.3 is associated with profound changes in global levels of both individual and combinatorial H3 methyl modifications. A subset of these modifications exhibit distinct relative abundances on H3 variants and remain stably enriched on H3.3 throughout the lifespan, suggesting a causal relationship between H3 variant replacement and age-dependent changes in H3 methylation. Furthermore, the H3.3 level is drastically reduced in human hepatocarcinoma cells as compared to nontumoral hepatocytes, suggesting the potential utility of the H3.3 relative abundance as a biomarker of abnormal cell proliferation activity. Overall, our study provides the first quantitative characterization of dynamic changes in H3 proteoforms throughout lifespan in mammals and suggests a role for H3 variant replacement in modulating H3 methylation landscape with age.
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