The 24-Hour Molecular Landscape After Exercise in Humans Reveals MYC is Sufficient for Muscle Growth

A detailed understanding of molecular responses to a hypertrophic stimulus in skeletal muscle leads to therapeutic advances aimed at promoting muscle mass. To decode the molecular factors regulating skeletal muscle mass, we utilized a 24-hour time course of human muscle biopsies after a bout of resistance exercise. Our findings indicate: 1) the DNA methylome response at 30 minutes corresponds to upregulated genes at 3 hours, 2) a burst of translation- and transcription-initiation factor-coding transcripts occurs between 3 and 8 hours, 3) changes to global protein-coding gene expression peaks at 8 hours, 4) ribosome-related genes dominate the mRNA landscape between 8 and 24 hours, 5) methylation-regulated MYC is a highly influential transcription factor throughout recovery. To test whether MYC is sufficient for hypertrophy, we periodically pulse MYC in skeletal muscle over four weeks. Transient MYC increases muscle mass and fiber size in the soleus of adult mice. We present a temporally resolved resource for understanding molecular adaptations to resistance exercise in muscle (http://data.myoanalytics.com) and suggest that controlled MYC doses promote the exercise-related hypertrophic transcriptional landscape.