ArticleClinical epigenetics2015
Replicative senescence is associated with nuclear reorganization and with DNA methylation at specific transcription factor binding sites.
Article in Clinical epigenetics, 2015. 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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45 citing papers in PubMed, 74 citations in OpenAlex.
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- Aging-related signature stratifies LUAD prognosis and uncovers senescence-induced chemoresistance via NF-κB/RELA activation.Respiratory research · 2025Article
- Epigenetic networks coordinate DNA methylation across the genome.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Interrogating the regulatory epigenome of cellular senescence.Cellular and molecular life sciences : CMLS · 2025Review
- Protocol for differentiating primary human small airway epithelial cells at the air-liquid interface.American journal of physiology. Lung cellular and molecular physiology · 2025Article
- Regulation of circadian gene activity in fibroblasts from ADHD patients through Rosiglitazone: a pilot study.Journal of neural transmission (Vienna, Austria : 1996) · 2025Article
- RNA sequencing identifiesCytotechnology · 2025Article
- Study Models forMicroorganisms · 2025Review
- Retarding human adipose-derived MSCs senescence and promoting tendon repair using cell sheet engineering with a histone methyltransferase inhibitor.Scientific reports · 2025Article
- An expedited screening platform for the discovery of anti-ageing compounds in vitro and in vivo.Genome medicine · 2024Article
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- Increased post-mitotic senescence in aged human neurons is a pathological feature of Alzheimer's disease.Cell stem cell · 2022Article
- Unveiling E2F4, TEAD1 and AP-1 as regulatory transcription factors of the replicative senescence program by multi-omics analysis.Protein & cell · 2022Article
- The functional impact of nuclear reorganization in cellular senescence.Briefings in functional genomics · 2022Review
- Alterations to Genome Organisation in Stem Cells, Their Differentiation and Associated Diseases.Results and problems in cell differentiation · 2022Article
- Translational control in cell ageing: an update.Biochemical Society transactions · 2021Review
- Adipose tissue senescence is mediated by increased ATP content after a short-term high-fat diet exposure.Aging cell · 2021Article
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPrimary cells enter replicative senescence after a limited number of cell divisions. This process needs to be considered in cell culture experiments, and it is particularly important for regenerative medicine. Replicative senescence is associated with reproducible changes in DNA methylation (DNAm) at specific sites in the genome. The mechanism that drives senescence-associated DNAm changes remains unknown - it may involve stochastic DNAm drift due to imperfect maintenance of epigenetic marks or it is directly regulated at specific sites in the genome.
resultsIn this study, we analyzed the reorganization of nuclear architecture and DNAm changes during long-term culture of human fibroblasts and mesenchymal stromal cells (MSCs). We demonstrate that telomeres shorten and shift towards the nuclear center at later passages. In addition, DNAm profiles, either analyzed by MethylCap-seq or by 450k IlluminaBeadChip technology, revealed consistent senescence-associated hypermethylation in regions associated with H3K27me3, H3K4me3, and H3K4me1 histone marks, whereas hypomethylation was associated with chromatin containing H3K9me3 and lamina-associated domains (LADs). DNA hypermethylation was significantly enriched in the vicinity of genes that are either up- or downregulated at later passages. Furthermore, specific transcription factor binding motifs (e.g. EGR1, TFAP2A, and ETS1) were significantly enriched in differentially methylated regions and in the promoters of differentially expressed genes.
conclusionsSenescence-associated DNA hypermethylation occurs at specific sites in the genome and reflects functional changes in the course of replicative senescence. These results indicate that tightly regulated epigenetic modifications during long-term culture contribute to changes in nuclear organization and gene expression.
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