Cell Metabolism - Acute Exercise Remodels Promoter Methylation in Human Skeletal Muscle

Cell Metabolism - Acute Exercise Remodels Promoter Methylation in Human Skeletal Muscle

Cell Metabolism, Volume 15, Issue 3, 405-411, 7 March 2012
Copyright © 2012 Elsevier Inc. All rights reserved.
10.1016/j.cmet.2012.01.001

Authors

Romain Barrès, Jie Yan, Brendan Egan, Jonas Thue Treebak, Morten Rasmussen, Tomas Fritz, Kenneth Caidahl, Anna Krook, Donal J. O'Gorman, Juleen R. ZierathSee Affiliations

• Highlights
• Transient promoter methylation occurs after an acute exercise
• Ex vivo muscle contraction mimics exercise-induced hypomethylation
• Caffeine mediates DNA hypomethylation in myocytes, implicating a role for Ca²⁺ release

Summary

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.