Interrelated but Not Time-Aligned Response in Myogenic Regulatory Factors Demethylation and mRNA Expression after Divergent Exercise Bouts

Abstract

Introduction: DNA methylation regulates exercise-induced changes in the skeletal muscle transcriptome. However, the specificity and the time course responses in the myogenic regulatory factors DNA methylation and mRNA expression after divergent exercise modes are unknown. Purpose: This study aimed to compare the time course changes in DNA methylation and mRNA expression for selected myogenic regulatory factors (MYOD1, MYF5, and MYF6) immediately after, 4 h after, and 8 h after a single bout of resistance exercise (RE), high-intensity interval exercise (HIIE), and concurrent exercise (CE). Methods: Nine healthy but untrained males (age, 23.9 ± 2.8 yr; body mass, 70.1 ± 14.9 kg; peak oxygen uptake [ VO 2peak ], 41.4 ± 5.2 mL•kg −1 •min −1 ; mean ± SD) performed a counterbalanced, randomized order of RE (4 Â 8-12 repetition maximum), HIIE (12 Â 1 min sprints at VO 2peak running velocity), and CE (RE followed by HIIE). Skeletal muscle biopsies (vastus lateralis) were taken before (REST) immediately (0 h), 4 h, and 8 h after each exercise bout. Results: Compared with REST, MYOD1, MYF5, and MYF6, mean methylation across all CpGs analyzed was reduced after 4 and 8 h in response to all exercise protocols (P < 0.05). Reduced levels of MYOD1 methylation were observed after HIIE and CE compared with RE (P < 0.05). Compared with REST, all exercise bouts increased mRNA expression over time (MYOD1 at 4 and 8 h, and MYF6 at 4 h; P < 0.05). MYF5 mRNA expression was lower after 4 h compared with 0 h and higher at 8 h compared with 4 h (P < 0.05). Conclusions: We observed an interrelated but not time-aligned response between the exercise-induced changes in myogenic regulatory factors demethylation and mRNA expression after divergent exercise modes. Despite divergent contractile stimuli, changes in DNA methylation and mRNA expression in skeletal muscle were largely confined to the late (4-8 h) recovery period and similar between the different exercise challenges.

Skeletal Muscle DNA Methylation and mRNA Responses to a Bout of Higher versus Lower Load Resistance Exercise in Previously Trained Men

“…The authors reported that CpG sites associated with several metabolic genes exhibited more robust demethylation responses to the higher intensity bout of change-of-direction running versus straight line running. Telles et al [48] more recently examined how resistance exercise, high-intensity interval exercise, or the combination of both affected the mRNA expression and DNA methylation of select myogenic regulatory factors (MYOD1, MYF5, and MYF6). All exercise protocols were reported to promote DNA demethylation of these genes 4 h and 8 h post-exercise, and the mRNA expression of MYOD1 and MYF6 were elevated 4 h following exercise.…”

“…Additionally, when acute and chronic methylome and transcriptome data were overlapped, ~40% of differentially expressed genes were shown to be associated with altered DNA methylation signatures [24]. Telles et al [48] more recently reported that an interrelated, but not time-aligned response, of myogenic regulatory factor gene demethylation and mRNA expression occurred up to 8 h following resistance exercise and other exercise modalities. However, their analyses were only limited to three genes, and it is notable that all these prior studies examined untrained participants.…”

Skeletal muscle DNA methylation and mRNA responses to a bout of higher versus lower load resistance exercise in previously trained men

“…Additionally, when acute and chronic methylome and transcriptome data were overlapped, ~40% of differentially expressed genes were shown to be associated with altered DNA methylation signatures [24]. Telles et al [47] more recently reported that an interrelated, but not time-aligned response, of myogenic regulatory factor gene demethylation and mRNA expression occurred up to 8 hours following resistance exercise and other exercise modalities. However, their analyses were only limited to three genes, and it is notable that all these prior studies examined untrained participants.…”

“…The authors reported that CpG sites associated with several metabolic genes exhibited more robust demethylation responses to the higher intensity bout of change-of-direction running versus straight line running. Telles et al [47] more recently examined how resistance exercise, high-intensity interval exercise, or the combination of both affected the mRNA expression and DNA methylation of select myogenic regulatory factors (MYOD1, MYF5, and MYF6). All exercise protocols were reported to promote DNA demethylation of these genes 4- and 8-hours post-exercise, and the mRNA expression of MYOD1 and MYF6 were elevated 4 hours following exercise.…”

The molecular athlete: exercise physiology from mechanisms to medals

“…In some studies, endurance training promoted the demethylation of genes involved in angiogenesis or oxidative metabolism, associated with increased gene transcription ( 442 , 443 ), whereas in others there was little effect of HIIT or resistance training on DNA methylation ( 444 ). A recent study reported that despite divergent contractile stimuli (HIIT, endurance and resistance exercise), changes in DNA methylation and mRNA expression in skeletal muscle were largely confined to the late (4–8 h) recovery period and similar between the different exercise challenges ( 445 ). Many of the discrepancies between investigations can likely be explained by the timing of the biopsy ( 446 ), with time course studies suggesting that some DNA methylation changes are retained for up to 48 h after the last training bout ( 442 , 443 ), returning to baseline levels after 72 h ( 444 ).…”