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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]
Citations
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Dnmt3b Deficiency in Myf5+-Brown Fat Precursor Cells Promotes Obesity in Female Mice
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BackgroundInfluentialEpigenetic changes due to physical activity
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BackgroundEwing, G. W. (2015) · Journal of Computer Science & Systems Biology · doi:10.4172/jcsb.1000172 · Cited by 11
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Liong, M. (2015) · Microbiology Monographs · doi:10.1007/978-3-319-23213-3 · Cited by 13
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Normand-Gravier, T., Solsona, R., Dablainville, V., Racinais, S., Borrani, F., Bernardi, H., & Sanchez, A. M. J. (2024) · European Journal of Applied Physiology · doi:10.1007/s00421-024-05642-9 · Cited by 12
“Recent investigations have revealed that endurance exercise provoked global and gene-specific changes in the methylation levels in skeletal muscle biopsies of healthy sedentary men (Barrès et al. 2012).”
Caporossi, D., & Dimauro, I. (2024) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2024.01.023 · Cited by 23
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“As the methylome operates at the interface between the genome and the environment [69], the methylation level may change in response to exercise [70, 71], diet [72], smoking [73, 74], and pollutants [75].”
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“Regions in genes involved in systemic or local inflammation [11] and glucose metabolism [11,12] were differentially methylated in blood and skeletal muscle in response to an acute bout of aerobic physical activity (one cycling session) [11] and long-term (6 months) aerobic physical activity interventions (spinning, ae…”
BackgroundConsistently High Level of Cardiorespiratory Fitness and Incidence of Type 2 Diabetes
Momma, H., Sawada, S. S., Lee, I.-M. M., Gando, Y., Kawakami, R., Terada, S., Miyachi, M., Kinugawa, C., Okamoto, T., Tsukamoto, K., et al. (2017) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000001319 · Cited by 20
Muscle Stem Cell and Physical Activity: What Point is the Debate at?
Ceccarelli, G., Benedetti, L., Arcari, M., Carubbi, C., & Galli, D. (2017) · Open Medicine · doi:10.1515/med-2017-0022 · Cited by 12
“[29] showed that acute exercise induced transient DNA demethylation in the promoter region of Peroxisome proliferator activated receptor gamma (Pparg), Peroxisome proliferator activated receptor gamma coactivator-1alpha (Ppargc-1α), Pyruvate dehydrogenase kinase 4 (Pdk4), and Peroxisome Proliferator activated receptor…”
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Neuroimaging as a potential biomarker to optimize psychiatric research and treatment
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SCFA Producing Gut Microbiota and its Effects on the Epigenetic Regulation of Inflammation
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“In contrast, Barres et al. [122] demonstrated that HIIT induces rapid DNA hypomethylation in skeletal muscle, suggesting that the timing and intensity of exercise critically influence the epigenetic response.”
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VMHdm/cSF-1 neuronal circuits regulate skeletal muscle PGC1-α via the sympathoadrenal drive
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The Genomic Context and Corecruitment of SP1 Affect ERRα Coactivation by PGC-1α in Muscle Cells
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PGC‐1α‐mediated Changes in Phospholipid Profiles of Exercise‐trained Skeletal Muscle
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“A recent study conducted by Barres et al.14 showed that acute aerobic exercise alters global and gene-specific promoter methylation in skeletal muscle suggesting that DNA hypomethylation is an early event in contraction-induced gene activation.”
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“Especially epigenetic regulation of genes highly involved in sports performances and exercise physiology, such as myocyte enhancer factor 2 (Potthoff et al. 2007) or slow-twitching type I myosin heavy chain (Pandorf et al. 2009, Barres et al. 2012) came into the focus of sports-related research.”
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“73 In a broader sense, epigenetic changes to DNA or chromatin structure can influence gene transcription independently of their primary sequences.”
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“Our data differ from previous work in whichMYOD1methylation was unaltered 3 h after an aerobic-based exercise bout (16).”
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“This is based on the physiological response of the human body to skeletal muscle contractions which increases muscle metabolism using DNA promoter methylation modifications to change and increase loci and expression of genes following exercises (Barrès et al., 2012).”
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“[6] A number of studies showed that enduring exercise is capable to modify the DNA methylation in several tissues[7–10] whereas, concerning the effect of an acute exercise on DNA methylation, Barrès et al[11] described that a single maximal exercise was capable to induce in humans hypomethylation of vastus lateralis m…”
BackgroundRetractedEpigenetics: Understanding How our Choices Lead to our Diseases
Grayson, S., de Leon, F. D., & Muscoplat, C. (2014) · Journal of Clinical Case Reports · doi:10.4172/2165-7920.1000447 · Cited by 5
“One well documented scientific example that has also gained popularity through the media, is exposure to Bisphenol A (BPA), a compound found in polycarbonate plastic that alters the epigenetic programming leading to endocrine disruption which can increase risk for diabetes, cancers, reproductive problems, early pubert…”
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“We speculate that potential epigenetic changes driven by EE might be linked to a major epigenetic modification - DNA methylation - that suppresses gene expression by modulating the access of the transcription machinery to the chromatin or by recruiting methyl binding proteins [44].”
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Zhou, F., Resendiz, M., & Lo, C. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-805388-1.00031-6 · Cited by 8
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“Nevertheless, few studies have found that PE-induced DNAm might be intensity dependent (2,9), whereas higher-intensity exercise induced DNA hypo-methylation (2).”
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“In addition, Barrès et al. (2012) found that acute high-intensity PA caused an immediate reduction of PPARGC1A promoter methylation, whereas no significant changes in methylation were found after low-intensity PA.”
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“Recent studies identified epigenetic modifications via DNA methylation/demethylation as a molecular means of regulating muscle PGC1a gene expression in exercise and type 2 diabetes (6, 7).”
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“Recent data has shown that epigenetic modification, transient DNA hypomethylation, of certain gene-specific promoter regions is an early event in exercise-induced gene activation, preceding increases in mRNA expression following acute exercise (Barres et al., 2012).”
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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