Sex- and skeletal muscle-specific gene expression response of histone 3 lysine 27-modifying enzymes by voluntary running in mice.

Skeletal muscle is highly plastic and capable of remodeling its contractile and metabolic properties depending on physical demands. Such remodeling requires modification of chromatin structure to support transcriptional activation and repression of gene programs. Chromatin dynamics depend, in part, on the acetylation and methylation of histone 3 lysine 27 (H3K27), which is controlled by several enzymes that add and remove these histone marks. Several histone post-translational modifications in muscle have been shown to be modulated by exercise. Here, we sought to examine whether major H3K27 regulators themselves are altered by endurance training. Male and female C57BL/6J mice were provided with voluntary running wheels for 6 weeks and compared to sex-matched sedentary controls with locked running wheels. We found that exercise altered gene expression of epigenetic machinery responsible for regulating acetylation and methylation enrichment in both a muscle- and sex-specific manner, including major H3K27 acetyltransferases and core components of the polycomb repressive complex-2. Our findings add to a growing body of evidence implicating H3K27 post-translational modifications, and thereby chromatin dynamics, as a mechanistic component of exercise-induced muscle remodeling.