US EPA

2281345 

Journal Article 

Acute Exercise Remodels Promoter Methylation in Human Skeletal Muscle 

Barres, R; Yan, Jie; Egan, B; Treebak, JT; Rasmussen, M; Fritz, T; Caidahl, K; Krook, A; O'Gorman, DJ; Zierath, JR 

2012 

Yes 

Cell Metabolism
ISSN: 1550-4131 

15 

3 

405-411 

English 

22405075 

10.1016/j.cmet.2012.01.001 

WOS:000301701400020 

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.