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Gene body DNA hydroxymethylation restricts magnitude of transcriptional changes during aging.

ABSTRACT: Gene body DNA hydroxymethylation restricts magnitude of transcriptional changes during aging.

PROVIDER: PRJNA912998 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR22764220_1.fastq.gz	Fastqsanger.gz
	SRR22764220_2.fastq.gz	Fastqsanger.gz
	SRR22764221_1.fastq.gz	Fastqsanger.gz
	SRR22764221_2.fastq.gz	Fastqsanger.gz
	SRR22764222_1.fastq.gz	Fastqsanger.gz

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Gene body DNA hydroxymethylation restricts magnitude of transcriptional changes during aging [hMeDIP]

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Gene body DNA hydroxymethylation restricts magnitude of transcriptional changes during aging [direct RNA-seq]

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Gene body DNA hydroxymethylation restricts magnitude of transcriptional changes during aging.

Project description: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. This SuperSeries is composed of the SubSeries listed below.

2023-08-08 | GSE221124 | GEO

Gene body DNA hydroxymethylation restricts magnitude of transcriptional changes during aging [hMeDIP]

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Gene body DNA hydroxymethylation restricts magnitude of transcriptional changes during aging [RNA-seq]

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Gene body DNA hydroxymethylation restricts magnitude of transcriptional changes during aging [direct RNA-seq]

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Gene body DNA hydroxymethylation restricts the magnitude of transcriptional changes during aging.

Project description:DNA hydroxymethylation (5hmC) is the most abundant oxidative derivative of DNA methylation (5mC) and is typically enriched at enhancers and gene bodies of transcriptionally active and tissue-specific genes. Although aberrant genomic 5hmC has been implicated in many age-related diseases, the functional role of the modification in aging remains largely unknown. Here, we report that 5hmC is stably enriched in multiple aged organs. Using the liver and cerebellum as model organs, we show that 5hmC accumulates in gene bodies associated with tissue-specific function and thereby restricts the magnitude of gene expression changes during aging. Mechanistically, we found that 5hmC decreases binding affinity of splicing factors compared to unmodified cytosine and 5mC, and is correlated with age-related alternative splicing events, suggesting RNA splicing as a potential mediator of 5hmCâ€™s transcriptionally restrictive function. Furthermore, we show that various age-related contexts, such as prolonged quiescence and senescence, are partially responsible for driving the accumulation of 5hmC with age. We provide evidence that this age-related function is conserved in mouse and human tissues, and further show that the modification is altered by regimens known to modulate lifespan. Our findings reveal that 5hmC is a regulator of tissue-specific function and may play a role in regulating longevity.

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Gene body DNA hydroxymethylation restricts the magnitude of transcriptional changes during aging.

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X-Ray induced DNA-Hydroxymethylation changes

Project description:In this study we addressed the question whether changes of DNA hydroxymethylation after X-ray irradiation occur in a random fashion or if they show preferences for specific regions or features. We did not only focus on gene loci and promotor sights but also on gene body hydroxymethylation alterations and associated changes in gene expression. A more profound insight into hydroxymethylation characteristics triggered by radiation could provide clues to mechanisms and consequences of cellular response to irradiation including the immediate consequence of DNA strand breaks associated with active DNA demethylation as well as the long term risk of tumorigenesis or other associated diseases.

2019-01-29 | GSE111437 | GEO

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