Acute exercise remodels promoter methylation in human skeletal muscle.

By R. Barrès, Jie Yan, B. Egan, J. T. Treebak, Morten Rasmussen, T. Fritz, K. Caidahl, A. Krook, D. O'Gorman, J. Zierath. Cell Metabolism, 2012

917 citations recorded by the source corpus.

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.

Subfields: Molecular Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/c11e2ea608ff1c09350fc4a6f0150e3991ed5f33

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Molecular Biology

1. J. Hawley
2. Michael J. Joyner
3. M. Hargreaves
4. J. Zierath
5. Steven R Smith
6. P. Dobrinić
7. L. Bočkor
8. V. Zoldoš

In Physiology

1. J. Hawley
2. Michael J. Joyner
3. M. Hargreaves
4. J. Zierath
5. S. Fried

Citations in the corpus

• A Six Months Exercise Intervention Influences the Genome-wide DNA Methylation Pattern in Human Adipose Tissue (2013, neutral): “Changes in DNA methylation have been suggested to be a biological mechanism behind the beneficial effects of physical activity [18,36].”
• Repurposing the CRISPR-Cas9 system for targeted DNA methylation (2016, background): “The reversible nature of epigenetic modifications including DNA methylation (17,18) has been already exploited by the use of epigenetic inhibitors (such as inhibitors of DNA methyltransferases or histone deacetylases) in cancer therapy in order to remodel the aberrant epigenetic landscape (19,20).”
• Integrative biology of exercise. (2014, positive): “Another level of regulation of mRNA and protein abundance by exercise involves alterations in DNA methylation status (Barrès et al., 2012), histone modifications (McGee and Hargreaves, 2011), and microRNA expression (Zacharewicz et al.”
• Sex differences in human adipose tissues – the biology of pear shape (2012, background): “Recent studies showing that acute exercise, overfeeding, and type 2 diabetes can modulate gene expression in skeletal muscle through epigenetic mechanisms [71-73] open the exciting scenario that lifestyle factors can interact with developmental programming to regulate adipose tissue mass and distrib”