Abstract
Exercise training causes epigenetic changes in skeletal muscle, although it is unclear how resistance exercise (RE) affects histone modifications. The present study was carried out to investigate the effects of acute RE and RE training on gene expression profiles and histone modifications in human skeletal muscle. Healthy male adults were assigned to acute RE (n = 9, age = 20.5±4.3yr, BMI = 28.0±6.8kg/m2) or RE training (n = 21, age = 23.7±2.5yr, BMI = 24.2±2.7kg/m2) groups. Biopsy samples were obtained from the vastus lateralis muscle before and three hours after a single bout of acute RE, or 3-days after 10 weeks of RE training. RNA sequencing analysis revealed that 153 genes with GO terms including muscle development, stress response, metabolism, cell death, and transcription factor were significantly up-regulated (+291% vs. pre-acute RE) upon acute RE. Expressions of these genes were also greater (+9.6% vs. pre-RE training, p<0.05) in RE trained subjects. Significant up-regulation of acetylated histone 3 (H3) (+235%) and H3 mono-methylated at lysine 4 (+290%) and tri-methylated at lysine 27 (+849%), whereas down-regulation of H3.3 variant (-39%) distributions relative to total H3 were observed at transcriptionally activated loci after acute RE compared to pre-acute RE levels. Interestingly, the distribution of acetylated H3 was found to be up-regulated as compared to the level of total H3 after RE training (+40%, p<0.05). These results indicate that a single bout of RE drastically alters both gene expressions and histone modifications in human skeletal muscle. It is also suggested that enhanced histone acetylation is closely related to up-regulation of gene expressions after RE training.
Highlights
Gain of exercise-induced effects on skeletal muscles differs between individuals
Results of Gene ontology (GO) analysis showed that the major GO terms including genes up-regulated upon acute resistance exercise (RE), were muscle development, stress response, metabolism, cell death, and transcription factor (Fig 3)
Nine biopsies were randomly chosen in Experiment 2, and three were selected for Chromatin immunoprecipitation (ChIP) and western blot analysis in both experiments
Summary
Begue et al [6] demonstrated that fiber type-specific DNA methylation in human skeletal muscle, showing CpG sites of genes selectively expressed in type 1 or IIa myosin heavy chain fibers were hypomethylated These data suggest that epigenetic regulation based on muscle fiber type characteristics affected the responsiveness of genes to exercise. We further reported that endurance exercise training decreased the responsiveness of genes to muscular unloading in association with enhanced incorporation of histone variant H3.3 into the nucleosomes in the plantaris muscle of rats. This indicates that endurance exercise training stimulated the turnover of histones [7], but it is currently unclear how RE affects the distribution of histones and their modification patterns in animal models. The present study is built upon the animal model literature, and aims to investigate the response of gene expression profiles and histone modifications in human muscle before and after acute RE and chronic RE training, respectively
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