期刊
AGING-US
卷 6, 期 7, 页码 545-563出版社
IMPACT JOURNALS LLC
DOI: 10.18632/aging.100678
关键词
senescence; gene expression; genome stability; H3K9 methylation; SUV39H1a
资金
- Alberta Cancer Foundation (ACF)
- Alberta Innovates - Health Solutions (AI-HS)
- US Department of Energy - Low Dose program (DoE)
- National Sciences and Engineering Research Council of Canada (NSERC)
- Canadian Institutes of Health Research (CIHR)
Cellular senescence has been associated with the age-dependent decline in tissue repair and regeneration, the increasing deterioration of the immune system, and the age-dependent increase in the incidence of cancer. Here, we show that senescence of human lung fibroblast WI-38 cells is associated with extensive changes to the gene expression profile, including the differential expression of transcriptional and epigenetic regulators. Among those, SUV39H1 was downregulated in senescent cells, correlated with a decrease in global H3K9 trimethylation, reduced H3K9me3 levels in repetitive DNA sequence regions such as satellites and transposable elements, and increased transcription of these repetitive DNA sequences. This indicates that SUV39H1 plays a role in limiting genomic instability in dividing cells and suggests that SUV39H1 downregulation may contribute to the establishment of senescence by increasing genomic instability. Additionally, the manipulation of SUV39H1 expression levels resulted in altered cell cycle distribution, suggesting a causal role of SUV39H1 in the establishment of cellular senescence. Thus, based on our findings and the results from previous reports, we propose a model in which SUV39H1 downregulation promotes the establishment of cellular senescence.
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