ArticleGenome biology2021
HDAC4 degradation during senescence unleashes an epigenetic program driven by AP-1/p300 at selected enhancers and super-enhancers.
Article in Genome biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 61 citations in OpenAlex.
- From cell to disease: Regulatory networks and mechanisms of super‑enhancers in aging (Review).Molecular medicine reports · 2026Review
- HMGA1-HP1β axis regulates premature aging in Hutchinson-Gilford progeria syndrome through chromatin remodeling.Nature communications · 2026Article
- Epigenetic dynamics of cellular senescence: From mechanistic insights to precision senotherapy.Chinese medical journal · 2026Review
- RPA hyperphosphorylation hinders the resolution of R-loops and G-quadruplex-associated R-loops during RAS-driven senescence.Nucleic acids research · 2026Article
- Review
- Class IIa HDACs forced degradation allows resensitization of oxaliplatin-resistant FBXW7-mutated colorectal cancer.Molecular oncology · 2026Article
- Neuroendocrine-associated epigenetic factors in cellular senescence: mechanisms and therapeutic implications.Biogerontology · 2026Review
- Dermal Fibroblast Senescence: The Central Hub of Skin Aging-From Intrinsic Dysfunction to Microenvironmental Remodeling.International journal of molecular sciences · 2026Review
- Natural Products as Anti-Senescence-Associated Secretory Phenotype (SASP) Agents.Current medicinal chemistry · 2026Review
- The controversial role of senescence-associated secretory phenotype (SASP) in cancer therapy.Molecular cancer · 2025Review
- HIFU-Driven Targeted Pyroptosis Therapy in Basal-Like Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Heterogeneity of Cellular Senescence, Senotyping, and Targeting by Senolytics and Senomorphics in Lung Diseases.International journal of molecular sciences · 2025Review
- Exploring the uncharted role of cell senescence in rare diseases.Orphanet journal of rare diseases · 2025Review
- The states of senescent cells.Biochemical Society transactions · 2025Review
- Cellular senescence in cancer: from mechanism paradoxes to precision therapeutics.Molecular cancer · 2025Review
- Class IIa HDACs Are Important Signal Transducers with Unclear Enzymatic Activities.Biomolecules · 2025Review
- Multiomics and cellular senescence profiling of aging human skeletal muscle uncovers Maraviroc as a senotherapeutic approach for sarcopenia.Nature communications · 2025Article
- FOXM1 expression reverts aging chromatin profiles through repression of the senescence-associated pioneer factor AP-1.Nature communications · 2025Article
- IRF1 is a core transcriptional regulatory circuitry member promoting AML progression by regulating lipid metabolism.Experimental hematology & oncology · 2025Article
- Valproic acid-induced teratogenicity is driven by senescence and prevented by Rapamycin in human spinal cord and animal models.Molecular psychiatry · 2025Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCellular senescence is a permanent state of replicative arrest defined by a specific pattern of gene expression. The epigenome in senescent cells is sculptured in order to sustain the new transcriptional requirements, particularly at enhancers and super-enhancers. How these distal regulatory elements are dynamically modulated is not completely defined.
resultsEnhancer regions are defined by the presence of H3K27 acetylation marks, which can be modulated by class IIa HDACs, as part of multi-protein complexes. Here, we explore the regulation of class IIa HDACs in different models of senescence. We find that HDAC4 is polyubiquitylated and degraded during all types of senescence and it selectively binds and monitors H3K27ac levels at specific enhancers and super-enhancers that supervise the senescent transcriptome. Frequently, these HDAC4-modulated elements are also monitored by AP-1/p300. The deletion of HDAC4 in transformed cells which have bypassed oncogene-induced senescence is coupled to the re-appearance of senescence and the execution of the AP-1/p300 epigenetic program.
conclusionsOverall, our manuscript highlights a role of HDAC4 as an epigenetic reader and controller of enhancers and super-enhancers that supervise the senescence program. More generally, we unveil an epigenetic checkpoint that has important consequences in aging and cancer.
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