title: Acute exercise remodels promoter methylation in human skeletal muscle.
abstract: DNA methylation is a covalent biochemical modification controlling chromatin structure and gene expression. Exercise elicits gene expression changes that trigger structural and metabolic adaptations in skeletal muscle. We determined whether DNA methylation plays a role in exercise-induced gene expression. Whole genome methylation was decreased in skeletal muscle biopsies obtained from healthy sedentary men and women after acute exercise. Exercise induced a dose-dependent expression of PGC-1α, PDK4, and PPAR-δ, together with a marked hypomethylation on each respective promoter. Similarly, promoter methylation of PGC-1α, PDK4, and PPAR-δ was markedly decreased in mouse soleus muscles 45 min after ex vivo contraction. In L6 myotubes, caffeine exposure induced gene hypomethylation in parallel with an increase in the respective mRNA content. Collectively, our results provide evidence that acute gene activation is associated with a dynamic change in DNA methylation in skeletal muscle and suggest that DNA hypomethylation is an early event in contraction-induced gene activation.
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska University Hospital, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
authors.forename: Romain
authors.initials: R
authors.lastname: Barrès
authors.forename: Jie
authors.initials: J
authors.lastname: Yan
authors.forename: Brendan
authors.initials: B
authors.lastname: Egan
authors.forename: Jonas Thue
authors.initials: JT
authors.lastname: Treebak
authors.forename: Morten
authors.initials: M
authors.lastname: Rasmussen
authors.forename: Tomas
authors.initials: T
authors.lastname: Fritz
authors.forename: Kenneth
authors.initials: K
authors.lastname: Caidahl
authors.forename: Anna
authors.initials: A
authors.lastname: Krook
authors.forename: Donal J
authors.initials: DJ
authors.lastname: O'Gorman
authors.forename: Juleen R
authors.initials: JR
authors.lastname: Zierath
mesh_terms: D000328:Adult; D000818:Animals; D019175:DNA Methylation / Q000235:genetics / Q000502:physiology; D015444:Exercise / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000378:metabolism*; D055815:Young Adult