An integrative analysis reveals coordinated reprogramming of the epigenome and the transcriptome in human skeletal muscle after training

Maléne E. Lindholm, Francesco Marabita, David Gomez-Cabrero, Helene Rundqvist, Tomas J. Ekström, Jesper Tegnér, Carl Johan Sundberg

Research output: Contribution to journalArticlepeer-review

177 Scopus citations

Abstract

Regular endurance exercise training induces beneficial functional and health effects in human skeletal muscle. The putative contribution to the training response of the epigenome as a mediator between genes and environment has not been clarified. Here we investigated the contribution of DNA methylation and associated transcriptomic changes in a well-controlled human intervention study. Training effects were mirrored by significant alterations in DNA methylation and gene expression in regions with a homogeneous muscle energetics and remodeling ontology. Moreover, a signature of DNA methylation and gene expression separated the samples based on training and gender. Differential DNA methylation was predominantly observed in enhancers, gene bodies and intergenic regions and less in CpG islands or promoters. We identified transcriptional regulator binding motifs of MRF, MEF2 and ETS proteins in the proximity of the changing sites. A transcriptional network analysis revealed modules harboring distinct ontologies and, interestingly, the overall direction of the changes of methylation within each module was inversely correlated to expression changes. In conclusion, we show that highly consistent and associated modifications in methylation and expression, concordant with observed health-enhancing phenotypic adaptations, are induced by a physiological stimulus.
Original languageEnglish (US)
Pages (from-to)1557-1569
Number of pages13
JournalEpigenetics
Volume9
Issue number12
DOIs
StatePublished - Jan 27 2014
Externally publishedYes

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