Acute Exercise Remodels Promoter Methylation in Human Skeletal Muscle

“Evidence has emerged to support a physiological role of non-CpG methylation (Lister et al., 2009; Ramsahoye et al., 2000; Woodcock et al., 1988), notably in stems cells, where drastic remodeling of the epigenome occurs (Bird, 2007).”

“DNAmethylation is thought to be mitotically stable, and hence environmental factors were assumed to be unlikely candidates to induce substantial and sustained changes in DNAmethylation in adult tissues (Reik et al., 2001).”

“, 1988), notably in stems cells, where drastic remodeling of the epigenome occurs (Bird, 2007).”

“Evidence is emerging that epigenetic modifications through DNA methylation contribute to the increased risk and development of metabolic disease by modifying the expression of genes controlling whole body energy and glucose homeostasis (Barrès et al., 2009; Klose and Bird, 2006).”

“DNA methylation is a major epigenetic modification that suppresses gene expression by modulating the access of the transcription machinery to the chromatin or by recruiting methyl binding proteins (Cedar and Bergman, 2009).”

“Digested DNA (4 mg) was used for a standard MeDIP assay as described (Weber et al., 2005) and 1–2 mg for methylcytosine capture.”

“Evidence has emerged to support a physiological role of non-CpG methylation (Lister et al., 2009; Ramsahoye et al., 2000; Woodcock et al., 1988), notably in stems cells, where drastic remodeling of the epigenome occurs (Bird, 2007).”

“DNA methyl transferases 3A and 3B (DNMT3A and DNMT3B, also called de novo methyl transferases) possess demethylase activity, but the biochemical sequence is unknown (Kangaspeska et al., 2008; Métivier et al., 2008).”

“Exercise increases the messenger RNA (mRNA) expression and protein levels of a plethora of genes regulating mitochondrial function and fuel usage, including PGC-1a, transcription factor A, mitochondrial (TFAM); peroxisome proliferator-activated receptor d (PPAR-d); and pyruvate dehydrogenase kinase, isoenzyme 4 (PDK4)…”

“(Coffey and Hawley, 2007).”

“Page 3/13 A 6-month exercise training increased the level of methylation in adipose tissue (Rönn et al. 2013) and decreased the level of global methylation in peripheral blood mononuclear cells (PBMC) (Dimauro et al. 2016) and muscle tissue (Barrès et al. 2012).”

“…2+ from the sarcoplasmic reticulum or entry of extracellular Ca 2+ , resulting in mitochondrial Ca 2+ overload and mitochondrial ROS emission, which ultimately results in muscle fatigue and dysfunction [13,17–19 Exercise significantly alters the DNA methylation profile of skeletal muscle [29–37].”

“[49] 2012 Self-controlled Study 14 sedentary and healthy participants Acute physical exercise promoted change in fatty acid gene transporters”

“Although resistance and endurance training lead to distinct cellular adaptation, there are several genes, including known regulatory factors, that are differentially expressed in response to both modalities, for example VEGFA, PDK4, PPARGC1A and FOXO3 (Barrès et al., 2012; Lindholm et al., 2014a; Raue et al., 2012).”

“To date, it is very clear that DNA methylation does not solely control exercise-induced gene expression (13) as there are other complex cellular transductional network systems which modify the DNA methylation (14).”

“Notably, chromatin remodeling through histone modifications may be linked to the increased regulation of gene transcription (see fig. 14, 15, 18, 19, 22, 23 and 24; Barrès et al., 2012).”

“Moreover, non-CpG methylation deserves more attention since it was associated with T2D [91], markers of obesity [318], and it was shown to be sensitive to acute exercise [93] and gastric bypass surgery [318].”

“In particular, the advent of next-generation sequencing (NGS) technology has transformed the analysis of gene expression profiles and DNA methylation patterns to a genome-wide tool for identifying exercise-induced genes and elucidating their roles (Barres et al. 2012; Park et al. 2012).”

“In healthy but inactive individuals, whole-genome methylation was decreased after an acute bout of exercise.(4) It was also reported that hypomethylation of the promoter region of key metabolic genes, and the subsequent expression of mRNA, was dependent on the intensity of the exercise.”

“For example, acute endurance exercise has been shown to demethylate promoters of key metabolic genes such as PGC-1 α, PDK4 , and PPARδ in human skeletal muscle, leading to their upregulated expression and improved metabolic adaptation [144].”

“…вісник Придніпров’я Науково-практичний журнал м'язових волокон, що розрізня-ються своїми скорочувальними і метаболічними характеристика-ми [3, 17, 18]: - І "Повільні" м'язові волокна (ПВ) повільно скорочуються, по-вільно стомлюються, в їх енерго-забезпеченні переважає анаероб-ний гліколіз.”

“more pronounced demethylation, meaning that exercise can induce a dose-dependent expression of certain genes.(2) Specifically, hypomethylation was noted on the promoter region of the following genes: PGC-1α, PDK4, and PPAR-δ.”