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Acute Exercise Remodels Promoter Methylation in Human Skeletal Muscle
Open accessAbstract
DNA methylation is a covalent biochemical modification controlling chromatin structure and gene expression. Exercise elicits gene expression changes that trigger structural and metabolic adaptations in skeletal muscle. We determined whether DNA methylation plays a role in exercise-induced gene expression. Whole genome methylation was decreased in skeletal muscle biopsies obtained from healthy sedentary men and women after acute exercise. Exercise induced a dose-dependent expression of PGC-1α, PDK4, and PPAR-δ, together with a marked hypomethylation on each respective promoter. Similarly, promoter methylation of PGC-1α, PDK4, and PPAR-δ was markedly decreased in mouse soleus muscles 45 min after ex vivo contraction. In L6 myotubes, caffeine exposure induced gene hypomethylation in parallel with an increase in the respective mRNA content. Collectively, our results provide evidence that acute gene activation is associated with a dynamic change in DNA methylation in skeletal muscle and suggest that DNA hypomethylation is an early event in contraction-induced gene activation.
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“A review of available data suggests that tonic immobility, peritraumatic dissociation, and dissociative PTSD may be mediated by a shared neural network involving amygdala deactivation, absence of sympathetically mediated arousal symptoms (decreased skin conductance and an absence of heart rate increases), parasympathetic activation (a decrease in heart rate in some studies, presumably reflecting a”
From Fear and the Defense Cascade (2015) · cites this paper as [121]
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“The muscle contraction that occurs during exercise also causes intracellular perturbations that disturb metabolic homeostasis, thereby promoting a broad range of adaptive responses and increasing overall resilience in response to stress.157,158”
From Fear and the Defense Cascade (2015) · cites this paper as [157]
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InfluentialEpigenetic regulation of aging: implications for interventions of aging and diseases
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“Previousworkwas able to detect an 10% (p 0.05) decrease in methylation of DNA within 20 min of acute exercise (Barrès et al., 2012).”
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“DNA methylation signatures are not static but can be remodeled by TFs (Stadler et al., 2011) and by environmental stimuli (Barrès et al., 2012).”
BackgroundObesity and Bariatric Surgery Drive Epigenetic Variation of Spermatozoa in Humans
Donkin, I., Versteyhe, S., Ingerslev, L. R., Qian, K., Mechta, M., Nordkap, L., Mortensen, B., Appel, E. V. R., Jørgensen, N., Kristiansen, V. B., et al. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.11.004 · Cited by 549
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BackgroundInfluentialSelf-citationThe evidence for functional non-CpG methylation in mammalian cells
Patil, V., Ward, R. L., & Hesson, L. B. (2014) · Epigenetics · doi:10.4161/epi.28741 · Cited by 214
“Also, acute bouts of exercise cause transient reductions in the levels of nonCpG methylation at the PGC-1α promoter, concomitant with increased PGC-1α expression.(40) Interestingly, a study of mitochondrial DNA methylation has also reported that ~50% of methylcytosine within the D-loop region, which contributes to the…”
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Hawley, J. A., Lundby, C., Cotter, J. D., & Burke, L. M. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.04.014 · Cited by 182
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“High-intensity exercise is a powerful stimulus affecting the content, location, and/or activity of nuclear proteins, and genes encoding mitochondrial proteins, leading to an increase in mitoPS (5, 30, 44, 49, 54).”
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“…acute aerobic exercise at 80% of maximal aerobic capacity (until 1674 KJ was expended) and a reduction in PPARd methylation 3 h post exercise, corresponding with reductions in their own gene expression (3 h post exercise for PGC-1a, PDK4 and PPAR-d, immediately post for TFAM) (Barres et al., 2012).”
BackgroundInfluentialExercise adaptations: molecular mechanisms and potential targets for therapeutic benefit
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“Hypermethylation and reduced expression of PGC1α is associated with decreased mitochondrial number and function in muscle (Barrès et al., 2009; 2012).”
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“One such modification is DNA cytosine methylation, which was found to be decreased overall in skeletal muscle samples from sedentary men and women following acute exercise (Barres et al. 2012).”
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“Several studies have examined the effect of exercise on the epigenome in skeletal muscle of healthy, obese, or individuals with T2D [78,93].”
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“Epigenetics A single muscle contraction is sufficient to induce hypomethylation of the promoter regions of key substrate metabolism genes, resulting in upregulated transcription and subsequent protein translation and action [31].”
BackgroundGenome-Wide Sperm DNA Methylation Changes After 3 Months of Exercise Training in Humans
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“exercise induces gene activation producing DNA hypomethylation on each respective promoter [50].”
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“It can be speculated that a change in DNA methylation might not result in altered expression levels when relevant A B C 0.0 0.2 0.4 0.6 0.8 1.0 T S S 15 00 T S S 15 00 T S S 15 00 T S S 20 0 B od y 3' U T R Probe position C WY14,643 F A B P 4 D N A m et h yl at io n ( B v al u e) 0 2 4 6 8 10 12 D -3 0 D -3 1 D -3 4 D…”
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“3,68 71 Physical activity also bolsters mediating immune proteins and gene expression 72,73 and more distal biologic aging end points, such as mitochondrial health and telomerase levels, 74 – 77 which are closely related to telomere maintenance.”
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“Each cell type possesses its own gene expression pattern, driven by a specific epigenetic signature, which may also produce cell heritable characteristics (5).”
BackgroundInfluentialEpigenetic flexibility in metabolic regulation: disease cause and prevention
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“PDK4 expression has been shown to be regulated by various metabolic stimuli (such as starvation, exercise, and diabetes), the transcription factors FOXO and E2F1 [20], and epigenetic mechanisms such as promoter methylation and histone acetylation [37,38].”
BackgroundAcute exercise remodels mitochondrial membrane interactions in mouse skeletal muscle
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“DNA methylation and histone acetylation) that can influence gene expression, molecular function and thereby influence VO2max training response [61, 66].”
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Block, T., & El-Osta, A. (2017) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2017.09.003 · Cited by 130
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Exercise: Putting Action into Our Epigenome
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“Furthermore, the quantification of DNA methylation at CpG sites related to genes involved in metabolism—peroxisome proliferator-activated receptor-c, coactivator 1-a (PPARGC1A), peroxisome proliferator-activated receptord (PPARD) and mitochondrial transcription factor-a (TFAM) revealed decreased DNA methylation with p…”
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“A number of attractive possibilities may explain this phenomenon; for instance, changes in DNA methylation (3) may silence/activate gene expression, and this may vary according to the training state.”
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Genome-wide quantification of the effects of DNA methylation on human gene regulation
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BackgroundInfluence of vitamin C and vitamin E on redox signaling: implications for exercise adaptations
Cobley, J. N., McHardy, H., Morton, J. P., Nikolaidis, M. G., & Close, G. L. (2015) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2015.03.018 · Cited by 118
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Epigenetics of type 2 diabetes mellitus and weight change — a tool for precision medicine?
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“Interestingly, 3-hour post-exercise, these promoters became re-methylated, demonstrating the dynamic epigenetic response to exercise in skeletal muscle [38].”
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“As an example, a bout of intense exercise can induce DNA hypomethylation at the PPARGC1a locus in human skeletal muscle within hours, followed by increased gene expression; these effects were reversed after resting (Barrès et al., 2012).”
BackgroundAn Epigenetic Role of Mitochondria in Cancer
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“However, while these mechanisms have emerged as regulators 467 of skeletal muscle adaptations to various physiological stimuli, such as exercise (21), epigenetic 468”
Background
Metadata
- Authors
- Barrès, R., Yan, J., Egan, B., Treebak, J. T., Rasmussen, M., Fritz, T., Caidahl, K., Krook, A., O'Gorman, D. J., & Zierath, J. R.
- Affiliations
- University of Copenhagen (DK)
- Karolinska University Hospital (SE)
- Corresponding author
- Zierath, Juleen R.
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2012-03
- Volume
- 15
- Issue
- 3
- Pages
- 405-411
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2113728034
- Cited by
- 965
- References
- 32
- Citations by year
- 2026: 65 · 2025: 64 · 2024: 61 · 2023: 39 · 2022: 67 · 2021: 73 · 2020: 53 · 2019: 67 · 2018: 75 · 2017: 79 · 2016: 65 · 2015: 77 · 2014: 76 · 2013: 75 · 2012: 28
- FWCI
- 32.94
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- DNA methylation, promoter hypomethylation, acute exercise, skeletal muscle, PGC-1α, PDK4, PPARδ, gene expression regulation, muscle contraction, caffeine, soleus muscle, L6 myotubes, epigenetic regulation
- MeSH terms
- Adult, Animals, Female, Humans, Male, Mice, Inbred C57BL, Exercise, Muscle, Skeletal, DNA Methylation, Mice, Young Adult
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