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Occean, James R; Yang, Na; Sun, Yan; Dawkins, Marshall S; Munk, Rachel; Belair, Cedric; Dar, Showkat; Anerillas, Carlos; Wang, Lin; Shi, Changyou; Dunn, Christopher; Bernier, Michel; Price, Nathan L; Kim, Julie S; Cui, Chang-Yi; Fan, Jinshui; Bhattacharyya, Moitrayee; De, Supriyo; Maragkakis, Manolis; de Cabo, Rafael; Sidoli, Simone; Sen, Payel
Nature communications, 07/2024, Letnik: 15, Številka: 1Journal Article
Abstract DNA hydroxymethylation (5hmC), the most abundant oxidative derivative of DNA methylation, is typically enriched at enhancers and gene bodies of transcriptionally active and tissue-specific genes. Although aberrant genomic 5hmC has been implicated in age-related diseases, its functional role in aging remains unknown. Here, using mouse liver and cerebellum as model organs, we show that 5hmC accumulates in gene bodies associated with tissue-specific function and restricts the magnitude of gene expression changes with age. Mechanistically, 5hmC decreases the binding of splicing associated factors and correlates with age-related alternative splicing events. We found that various age-related contexts, such as prolonged quiescence and senescence, drive the accumulation of 5hmC with age. We provide evidence that this age-related transcriptionally restrictive function is conserved in mouse and human tissues. Our findings reveal that 5hmC regulates tissue-specific function and may play a role in longevity.
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in: SICRIS
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