Editors' ChoiceMetabolism

Pumping Iron Alters DNA Methylation

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Science Translational Medicine  07 Aug 2013:
Vol. 5, Issue 197, pp. 197ec132
DOI: 10.1126/scitranslmed.3007134

Epigenetic modifications of DNA are thought to be a mechanism by which gene expression is altered, resulting in changes in phenotypic traits. One of the easiest ways to assay epigenetic markers is DNA methylation. This can be determined by bisulfite treatment of DNA, which converts cytosine residues to uracil but leaves methylated cytosine unaffected. In new work, Rönn and colleagues report changes in DNA methylation in adipose tissue in healthy, sedentary men after 6 months of exercise. They nominate ~7600 genes with altered methylation with a false discovery rate of 0.05. Concurrently, about one-third of these genes show mRNA expression differences in the same individuals. For genes with evidence of differential methylation and expression, 61% showed inverse relationships between these two properties, which is consistent with the concept that average decreases in methylation yield increases in gene expression.

Over the course of 6 months, the authors also collected a range of phenotypic data and show nominal reductions in waist circumference, waist/hip ratio, pulse, diastolic blood pressure, and maximum oxygen intake. These results are consistent with the positive impact of exercise on a range of metabolic phenotypes.

With respect to translation, this approach holds promise for detailing the biological changes that occur as a consequence of an effective intervention. By assessing the DNA methylation and gene expression changes that occur in adipose tissue after exercise, the authors have pinpointed a set of genes that can be further evaluated to identify biological processes that underlie the positive benefits of exercise. Furthermore, the authors highlight the overlap between previously identified genes from genome-wide association studies of obesity and type II diabetes including KCNQ1 and TCF7L2, suggesting that the interpretation of identified genetic variants may be enhanced by studying epigenetic changes in genes.

T. Rönn et al., A six months exercise intervention influences the genome-wide DNA methylation pattern in human adipose tissue. PLoS Genet. 9 e1003572, (2013). [Full Text]

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