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Ablation of DNA-methyltransferase 3A in skeletal muscle does not affect energy metabolism or exercise capacity

ABSTRACT: Ablation of DNA-methyltransferase 3A in skeletal muscle does not affect energy metabolism or exercise capacity

PROVIDER: PRJNA639065 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12003800.fastq.gz	Fastqsanger.gz
	SRR12003801.fastq.gz	Fastqsanger.gz
	SRR12003802.fastq.gz	Fastqsanger.gz
	SRR12003803.fastq.gz	Fastqsanger.gz
	SRR12003804.fastq.gz	Fastqsanger.gz

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Ablation of DNA-methyltransferase 3A in skeletal muscle does not affect energy metabolism or exercise capacity [RRBS]

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Ablation of DNA-methyltransferase 3A in skeletal muscle does not affect energy metabolism or exercise capacity [RRBS]

Project description:Skeletal muscle can undergo large transcriptional changes in response to environmental stimuli such as diet or exercise in order to adapt to energetic demands. This remodelling has been associated with changes in muscle DNA methylation potentially regulating gene transcription. Despite abundant evidence that environmental stimuli can alter muscle DNA methylation, the mechanisms by which DNA methylation machinery respond to these stimuli and whether these have a physiological impact is still unclear. Therefore, we decided to investigate the importance of de novo DNA methylation on muscle methylation and function. We generated muscle specific DNMT3a knockout mice (mDKO) and investigated the impact of ablating DNMT3a in muscle on muscle DNA methylation, exercise capacity and energy metabolism. Loss of DNMT3a reduced DNA methylation in muscle over multiple genomic contexts and altered the transcription of genes known to be influenced by DNA methylation. However, mDKO mice had a similar exercise capacity and whole-body energy metabolism as WT mice. Similarly, loss of DNMT3a did not alter muscle mitochondrial function or the transcriptional response to exercise however did increase the expression of genes involved in muscle development. These data suggest that DNMT3a does not have a large role in the function of mature muscle although a role in muscle development and differentiation is still likely.

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Ablation of DNA-methyltransferase 3A in skeletal muscle does not affect energy metabolism or exercise capacity.

Project description:In response to physical exercise and diet, skeletal muscle adapts to energetic demands through large transcriptional changes. This remodelling is associated with changes in skeletal muscle DNA methylation which may participate in the metabolic adaptation to extracellular stimuli. Yet, the mechanisms by which muscle-borne DNA methylation machinery responds to diet and exercise and impacts muscle function are unknown. Here, we investigated the function of de novo DNA methylation in fully differentiated skeletal muscle. We generated muscle-specific DNA methyltransferase 3A (DNMT3A) knockout mice (mD3AKO) and investigated the impact of DNMT3A ablation on skeletal muscle DNA methylation, exercise capacity and energy metabolism. Loss of DNMT3A reduced DNA methylation in skeletal muscle over multiple genomic contexts and altered the transcription of genes known to be influenced by DNA methylation, but did not affect exercise capacity and whole-body energy metabolism compared to wild type mice. Loss of DNMT3A did not alter skeletal muscle mitochondrial function or the transcriptional response to exercise however did influence the expression of genes involved in muscle development. These data suggest that DNMT3A does not have a large role in the function of mature skeletal muscle although a role in muscle development and differentiation is likely.

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