Acute exercise remodels promoter methylation in human skeletal muscle

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

    502 Citations (Scopus)

    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.

    Original languageEnglish
    JournalCell Metabolism
    Volume15
    Issue number3
    Pages (from-to)405-11
    Number of pages7
    ISSN1550-4131
    DOIs
    Publication statusPublished - 7 Mar 2012

    Keywords

    • Adult
    • Animals
    • DNA Methylation
    • Exercise
    • Female
    • Humans
    • Male
    • Mice
    • Mice, Inbred C57BL
    • Muscle, Skeletal
    • Young Adult

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