title: Changes in the leukocyte methylome and its effect on cardiovascular-related genes after exercise.
abstract: Physical exercise has proven cardiovascular benefits, yet there is no clear understanding of the related molecular mechanisms leading to this. Here we determined the beneficial epigenetic effects of exercise after sprint interval training, a form of exercise known to improve cardiometabolic health. We quantified genome-wide leukocyte DNA methylation of 12 healthy young (18-24 yr) men before and after 4 wk (thrice weekly) of sprint interval training using the 450K BeadChip (Illumina) and validated gene expression changes in an extra seven subjects. Exercise increased subjects' cardiorespiratory fitness and maximal running performance, and decreased low-density lipoprotein cholesterol concentration in conjunction with genome-wide DNA methylation changes. Notably, many CpG island and gene promoter regions were demethylated after exercise, indicating increased genome-wide transcriptional changes. Among genes with DNA methylation changes, epidermal growth factor (EGF), a ligand of the epidermal growth factor receptor known to be involved in cardiovascular disease, was demethylated and showed decreased mRNA expression. Additionally, we found that in microRNAs miR-21 and miR-210, gene DNA methylation was altered by exercise causing a cascade effect on the expression of the mature microRNA involved in cardiovascular function. Our findings demonstrate that exercise alters DNA methylation in circulating blood cells in microRNA and protein-coding genes associated with cardiovascular physiology.
authors.affiliation: Faculty of Science and Technology, Federation University Australia, Ballarat, Victoria, Australia; and.
authors.forename: Joshua
authors.initials: J
authors.lastname: Denham
authors.affiliation: Faculty of Health, Federation University Australia, Ballarat, Victoria, Australia.
authors.forename: Brendan J
authors.initials: BJ
authors.lastname: O'Brien
authors.affiliation: Faculty of Science and Technology, Federation University Australia, Ballarat, Victoria, Australia; and.
authors.forename: Francine Z
authors.initials: FZ
authors.lastname: Marques
authors.affiliation: Faculty of Science and Technology, Federation University Australia, Ballarat, Victoria, Australia; and f.charchar@federation.edu.au.
authors.forename: Fadi J
authors.initials: FJ
authors.lastname: Charchar
mesh_terms: D000328:Adult; D002319:Cardiovascular System / Q000378:metabolism*; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D004815:Epidermal Growth Factor / Q000378:metabolism; D044127:Epigenesis, Genetic / Q000235:genetics; D066246:ErbB Receptors / Q000378:metabolism; D015444:Exercise / Q000502:physiology*; D015870:Gene Expression / Q000235:genetics*; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D055815:Young Adult
chemical_list: D008077:Lipoproteins, LDL; C524940:MIRN21 microRNA, human; C543800:MIRN210 microRNA, human; D035683:MicroRNAs; D004815:Epidermal Growth Factor; D066246:ErbB Receptors
keywords: DNA methylation; cholesterol; epigenetics; microRNA; sprint interval training