text: Endurance exercise-induced alteration to gene expression by DNA methylation or demethylation
  Endurance muscle training also alters muscle gene expression through epigenetic DNA methylation or de-methylation of CpG sites within enhancers.  In a study by Lindholm et al., twenty-three 27-year-old, sedentary, male and female volunteers had endurance training on only one leg during three months. The other leg was used as an untrained control leg. Skeletal muscle biopsies from the vastus lateralis were taken both before training began and 24 hours after the last training session from each of the legs. The endurance-trained leg, compared to the untrained leg, had significant DNA methylation changes at 4,919 sites across the genome. The sites of altered DNA methylation were predominantly in enhancers. Transcriptional analysis, using RNA sequencing, identified 4,076 differentially expressed genes.
  The transcriptionally upregulated genes were associated with enhancers that had a significant decrease in DNA methylation, while transcriptionally downregulated genes were associated with enhancers that had increased DNA methylation. In this study, the differentially methylated positions in enhancers with increased methylation were mainly associated with genes involved in structural remodeling of the muscle and glucose metabolism. The differentially decreased methylated positions in enhancers were associated with genes functioning in inflammatory/immunological processes and transcriptional regulation.