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Impact of Voluntary Wheel Running on Gene Expression of Histone 3 Lysine 27-Modifying Enzymes in Mouse Skeletal Muscle

Gamu, D.; Cameron, M.; Jalil, Y.; Zouaoui, I.; Sangha, J.; Kim, J.

2025-11-10 physiology
10.1101/2025.11.07.687293 bioRxiv
Show abstract

Skeletal muscle is highly plastic and capable of remodelling its contractile and metabolic properties depending on physical demands. Such remodelling requires modification of chromatin structure to support transcriptional activation and suppression of gene programs. Chromatin dynamics depend, in part, on the acetylation and methylation of histone 3 lysine 27 (H3K27), which is controlled by several H3K27-specific acetyltransferases, deacetylases, methyltransferases and demethylases. Several histone post-translational modifications in muscle have been shown to be modulated by exercise. Here, we sought to examine whether major H3K27 regulators 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. Gene expression of various slow/oxidative and fast/glycolytic skeletal muscles was then measured. We found voluntary running induced modest changes in H3K27 acetyltransferases, along with several components of the polycomb-repressive complex 2 in a muscle- and sex-specific manner. Our findings indicate that the capacity for both acetylation and methylation of H3K27 is modulated by chronic endurance exercise, suggesting that chromatin dynamics are a mechanistic component of exercise-induced muscle remodelling.

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