Acute exercise remodels promoter methylation in human skeletal muscle

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-1alpha, PDK4, and PPAR-delta, together with a marked hypomethylation on each respective promoter. Similarly, promoter methylation of PGC-1alpha, PDK4, and PPAR-delta 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.

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Fysiologi hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Physiology hsv//eng
Adult
Animals
DNA Methylation/genetics/physiology
Exercise/*physiology
Female
Humans
Male
Mice
Mice
Inbred C57BL
Muscle
Skeletal/*metabolism
Young Adult

Yan, J. (author)
Egan, B.Karolinska Institutet (author)
Treebak, J. T. (author)
Rasmussen, M. (author)
Fritz, T. (author)
Caidahl, Kenneth,1949Karolinska Institutet,Gothenburg University,Göteborgs universitet,Extern,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,External,Institute of Medicine, Department of Molecular and Clinical Medicine(Swepub:gu)xcaike (author)
Krook, A.Karolinska Institutet (author)
O'Gorman, D. J. (author)
Zierath, J. R.Karolinska Institutet (author)
Karolinska InstitutetExtern (creator_code:org_t)

By the author/editor: Barres, R.; Yan, J.; Egan, B.; Treebak, J. T.; Rasmussen, M.; Fritz, T.; show more...; Caidahl, Kenneth ...; Krook, A.; O'Gorman, D. J.; Zierath, J. R.; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Physiology

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