Investigating the Role of Selected Epigenetic Silencing Marks in Determining Mouse Skeletal Muscle Oxidative Phenotype

Epigenetic regulation of gene expression supports skeletal muscle phenotypic plasticity. The role of epigenetic silencing marks in maintaining muscle phenotype and in supporting muscle plasticity remains unknown. This study aims to characterize whether silencing marks established by Mdm2 and EZH2 play a role in determining the muscle oxidative phenotype at rest and after training. In sedentary C57Bl/6 female mice, the soleus muscle showed higher protein levels of Mdm2 and H3K27me3, and lower levels of EZH2 compared to glycolytic muscles. 9 weeks of endurance exercise training changed the protein levels of Mdm2, EZH2, and H3K27me3 in a muscle-specific manner in C57Bl/6 mice. Differentiation of C2C12 myoblasts depleted EZH2 protein levels, and increased the protein levels of Mdm2 and H3K27me3. Overall, our study shows that phenotypically different muscles show a different relative abundance of silencing marks. Endurance training may also affect the presence of silencing marks.