A recent publication from our group (finally online) in collaboration with scientist at the Physiology department, show that endurance training alter the DNA methylation profile in skeletal muscle.
We have adopted an integrative approach to investigate the impact of an environmental lifestyle intervention on the epigenome and transcriptome of human skeletal muscle. This is highly important, since regular endurance training induces extensive beneficial effects on skeletal muscle and it contributes to the prevention and treatment of a multitude of some of the most common diseases, e.g. cardiovascular disease, type II diabetes and several forms of cancer. The relationship between specific differential skeletal muscle DNA methylation and gene expression after long-term endurance training is not completely clarified. This human study provides novel insights about the mechanisms underlying the massive functional and health benefits of regular, long-term exercise, supporting the contribution of the epigenome to training response as a mediator between genes and environment.
We have combined a highly controlled prospective study design with a comprehensive bioinformatics analysis integrating transcriptional and epigenomic data at a global level and with single-base resolution. We show that a physiological stimulus can induce small but highly consistent modifications in DNA methylation that are associated to gene expression changes concordant with the observed phenotypic adaptation. This association provides a putative mechanism for the variability in transcriptional and adaptive response to physical activity, given the coordinated modulation that we observe in the proper in vivo context. Distinct ontologies from the sites changing in methylation strongly suggest a non-random effect across the genome. We also applied network-based approach to visualize and analyze the transcriptional changes and connect the associated methylation changes.
About 20% of the differentially expressed genes were affected by methylation changes. The modifications mainly occurred in regulatory enhancer regions, and less in promoters, a novel finding in the context of tissue adaptation to a physiological stimulus in humans. We also identified known binding domains for important transcription factors in close proximity to the differentially methylated sites, indicating that training induces methylation changes relevant for regulation of transcription.
Our study provides a valuable resource in the fields of human exercise physiology and environmental epigenomics because we are able to establish a link between the physiological adaptation of human skeletal muscle to a health-beneficial intervention, and molecular changes in the epigenome and transcriptome.
Published on figshare (http://dx.doi.org/10.6084/m9.figshare.1239050)
An integrative analysis reveals coordinated reprogramming of the epigenome and the transcriptome in human skeletal muscle after training.
Published in Epigenetics
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