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Exercise training alters DNA methylation patterns in genes related to muscle growth and differentiation in mice

  • The adaptive response of skeletal muscle to exercise training is tightly controlled and therefore requires transcriptional regulation. DNA methylation is an epigenetic mechanism known to modulate gene expression, but its contribution to exercise-induced adaptations in skeletal muscle is not well studied. Here, we describe a genome-wide analysis of DNA methylation in muscle of trained mice (n = 3). Compared with sedentary controls, 2,762 genes exhibited differentially methylated CpGs (P < 0.05, meth diff >5%, coverage > 10) in their putative promoter regions. Alignment with gene expression data (n = 6) revealed 200 genes with a negative correlation between methylation and expression changes in response to exercise training. The majority of these genes were related to muscle growth and differentiation, and a minor fraction involved in metabolic regulation. Among the candidates were genes that regulate the expression of myogenic regulatory factors (Plexin A2) as well as genes that participate in muscle hypertrophy (Igfbp4) and motorThe adaptive response of skeletal muscle to exercise training is tightly controlled and therefore requires transcriptional regulation. DNA methylation is an epigenetic mechanism known to modulate gene expression, but its contribution to exercise-induced adaptations in skeletal muscle is not well studied. Here, we describe a genome-wide analysis of DNA methylation in muscle of trained mice (n = 3). Compared with sedentary controls, 2,762 genes exhibited differentially methylated CpGs (P < 0.05, meth diff >5%, coverage > 10) in their putative promoter regions. Alignment with gene expression data (n = 6) revealed 200 genes with a negative correlation between methylation and expression changes in response to exercise training. The majority of these genes were related to muscle growth and differentiation, and a minor fraction involved in metabolic regulation. Among the candidates were genes that regulate the expression of myogenic regulatory factors (Plexin A2) as well as genes that participate in muscle hypertrophy (Igfbp4) and motor neuron innervation (Dok7). Interestingly, a transcription factor binding site enrichment study discovered significantly enriched occurrence of CpG methylation in the binding sites of the myogenic regulatory factors MyoD and myogenin. These findings suggest that DNA methylation is involved in the regulation of muscle adaptation to regular exercise training.show moreshow less

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Author details:Timo Kanzleiter, Markus Jaehnert, Gunnar Schulze, Joachim SelbigGND, Nicole Hallahan, Robert Wolfgang Schwenk, Annette SchürmannORCiDGND
DOI:https://doi.org/10.1152/ajpendo.00289.2014
ISSN:0193-1849
ISSN:1522-1555
Pubmed ID:https://pubmed.ncbi.nlm.nih.gov/25805191
Title of parent work (English):American journal of physiology : Endocrinology and metabolism
Publisher:American Chemical Society
Place of publishing:Bethesda
Publication type:Article
Language:English
Year of first publication:2015
Publication year:2015
Release date:2017/03/27
Tag:DNA methylation; muscle development; regular exercise training
Volume:308
Issue:10
Number of pages:9
First page:E912
Last Page:E920
Funding institution:German Ministry of Education and Research (BMBF: DZD) [01GI0922, 01GI0925]; State of Brandenburg; Leibniz Association [SAW-FBN-2013-3]
Organizational units:Mathematisch-Naturwissenschaftliche Fakultät / Institut für Biochemie und Biologie
Peer review:Referiert
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