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Gene body DNA hydroxymethylation restricts the magnitude of transcriptional changes during aging.
- Source :
- Nature Communications; 7/28/2024, Vol. 15 Issue 1, p1-22, 22p
- Publication Year :
- 2024
-
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.DNA hydroxymethylation (5hmC) is typically altered in age-related diseases. Here, the authors show that 5hmC accumulates in gene bodies, partially due to prolonged quiescence, and restricts the magnitude of transcriptional changes with age. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 15
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Nature Communications
- Publication Type :
- Academic Journal
- Accession number :
- 178748342
- Full Text :
- https://doi.org/10.1038/s41467-024-50725-y