Histone Modification: A Mechanism for Regulating Skeletal Muscle Characteristics and Adaptive Changes

Epigenetics is getting increased attention in the analysis of skeletal muscle adaptation to physiological stimuli. In this review, histone modifications in skeletal muscles and their role in the regulation of muscle characteristics and adaptive changes are highlighted. The distribution of active histone modifications, such as H3K4me3 and H3 acetylation, largely differs between fast- and slow-twitch muscles. It is also indicated that the transcriptional activity in response to exercise differs in these muscle types. Histone turnover activated by exercise training leads to loosening of nucleosomes, which drastically enhances gene responsiveness to exercise, indicating that the exercise training transforms the chromatin structure to an active status. Furthermore, histone modifications play a critical role in preserving the stem cell lineage in skeletal muscle. Lack of lysine-specific demethylase 1 in satellite cells promotes the differentiation into brown adipocytes during muscle regeneration after injury. H4K20me2, which promotes the formation of heterochromatin, is necessary to repress MyoD expression in the satellite cells. These observations indicate that histone modification is a platform that characterizes skeletal muscles and may be one of the factors regulating the range of adaptive changes in these muscles.