section_path: Exercise-trained effects are mediated by epigenetic mechanisms/Exercise-induced alteration to gene expression by DNA methylation or demethylation
section_name: Exercise-induced alteration to gene expression by DNA methylation or demethylation
paragraph_text: Exercise-induced alteration to gene expression by DNA methylation or demethylation
  
  Endurance muscle training alters muscle gene expression by epigenetic DNA methylation or de-methylation of CpG sites within enhancers.
  
  In a study by Lindholm et al., twenty-three individuals who were about 27 years old and sedentary volunteered to have endurance training on only one leg during 3 months. The other leg was used as an untrained control leg. The training consisted of one-legged knee extension training for 3 month (45 min, 4 sessions per week). Skeletal muscle biopsies from the vastus lateralis (a thigh muscle) 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. Increased methylation was mainly associated with genes involved in structural remodeling of the muscle and glucose metabolism. Enhancers with decreased methylation were associated with genes functioning in inflammatory or immunological processes and in transcriptional regulation.