Wednesday, 21 March 2012

Acute Exercise Remodels Promoter Methylation in Human Skeletal Muscle

We all know that there's only one way to lose weight and that's through regular exercise. A very recent study has suggested that it not only drops the kilos but also alters gene expression and chromatin structure in fat cells. The study published in the March issue of Cell Metabolism conducted experiments to test their hypothesis that physical stressors, in this case acute exercise which is already identified in body energy adjustments and glucose homeostasis, rapidly alters DNA methylation in skeletal muscle (Barrѐs et al, 2012). The results of their experiments show that acute gene activation is associated with a dynamic change in DNA methylation in skeletal muscle. It also suggests that DNA hypo-methylation is an early event in contraction-induced gene activation as a result of physical stress (Barrѐs et al, 2012).     

DNA methylation is a key adjustment that suppresses gene expression by controlling the access of the transcription machinery to the chromatin or by recruiting methyl binding proteins (Cedar and Bergman, 2009). Put simply, it is an important process that occurs in all higher animals that allows normal development and cellular differentiation. Skeletal muscle is distinguished by a high degree of plasticity in its adaptive response to environmental stressors that challenge the structural and metabolic demands of the tissue. Muscle contraction through physical exercise drives adaptive responses to improve metabolic efficiency, oxidative capacity, and contractile activity by altering gene expression profiles and protein levels (Coffey and Hawley, 2007). It has been seen in a number of previous studies that exercise increases mRNA expression and protein levels of many genes related to mitochondrial function and fuel usage. Until now it was unknown whether DNA methylation played a role in controlling these genomic alterations.

During the study, the effects of a single bout of strenuous exercise were studied using methylated DNA capture, followed by quantitative PCR and bisulfite sequencing. The participants were men and women aged 24-26 that usually led sedentary lifestyles. Biopsies were carried out on vastus lateralis skeletal muscle both before and after the bout of exercise, 1 hour to be exact. Using methylated DNA Immunoprecitation, which is a purification technique, followed by quantitative PCR they found that captured methylated promoters for metabolic genes were lower after acute exercise, whereas muscle-specific transcription factors, including MYOD1 and MEF2A, as well GAPDH, were unchanged. These results provide evidence to suggest that acute exercise induces gene-specific DNA hypomethylation in human skeletal muscle. A 2010 study showed that aerobic exercise intensity drives gene transcription in a dose-dependent manner (Egan et a., 2010). So the team also incorporated this into their study, determining whether the exercise-induced decrease in promoter methylation was dependent on exercise intensity. A dose-response and time-course analysis of DNA methylation was conducted in the same way but the participants exercise routines were don’t at either 40% (low-intensity) or 80% (high-intensity) of maximal aerobic capacity. The results suggest that DNA methylation is a component of the exercise-induced effect on expression of these genes (Barrѐs et al, 2012). 

Main Paper: 
Barrès, R. et al. (2012) Acute Exercise Remodels Promoter Methylation in Human Skeletal Muscle. Cell Metabolism, Volume 15, Issue 3, 405-411.  DOI: 10.1016/j.cmet.2012.01.001

Other References:
Cedar, H., and Bergman, Y. (2009)  Linking DNA methylation and histone modification: patterns and paradigms. Nat. Rev. Genet. 10, 295–304. 
Coffey, V.G., and Hawley, J.A. (2007) The molecular bases of training adaptation. Sports Med. 37, 737–763. 
Jaenisch, R.; Bird, A. (2003). "Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals". Nature genetics 33: 245–254. 


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