Exercise-induced histone modifications in human skeletal muscle
Open accessAbstract
Skeletal muscle adaptations to exercise confer many of the health benefits of physical activity and occur partly through alterations in skeletal muscle gene expression. The exact mechanisms mediating altered skeletal muscle gene expression in response to exercise are unknown. However, in recent years, chromatin remodelling through epigenetic histone modifications has emerged as a key regulatory mechanism controlling gene expression in general. The purpose of this study was to examine the effect of exercise on global histone modifications that mediate chromatin remodelling and transcriptional activation in human skeletal muscle in response to exercise. In addition, we sought to examine the signalling mechanisms regulating these processes. Following 60 min of cycling, global histone 3 acetylation at lysine 9 and 14, a modification associated with transcriptional initiation, was unchanged from basal levels, but was increased at lysine 36, a site associated with transcriptional elongation. We examined the regulation of the class IIa histone deacetylases (HDACs), which are enzymes that suppress histone acetylation and have been implicated in the adaptations to exercise. While we found no evidence of proteasomal degradation of the class IIa HDACs, we found that HDAC4 and 5 were exported from the nucleus during exercise, thereby removing their transcriptional repressive function. We also observed activation of the AMP-activated protein kinase (AMPK) and the calcium-calmodulin-dependent protein kinase II (CaMKII) in response to exercise, which are two kinases that induce phosphorylation-dependent class IIa HDAC nuclear export. These data delineate a signalling pathway that might mediate skeletal muscle adaptations in response to exercise.
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Chronic activation of AMPK and expression induction of PGC1α, MEF2, NRF-1, NRF-2, and nuclear expulsion of histone deacetylase 4 and 5 can lead to higher mitochondrial volume density and improved mitochondrial quality.
“A higher mitochondrial volume density and improved mitochondrial quality can be seen as consequences of chronic activation of AMPK and expression induction of PGC1α, myocyte-specific enhancer factor 2 (MEF2), NRF-1 and NRF-2, and nuclear expulsion of histone deacetylase 4 and 5 (41, 222, 224).”
From Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease (2018) · cites this paper as [224]
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- Authors
- McGee, S. L., Fairlie, E., Garnham, A. P., & Hargreaves, M.
- Affiliations
- Deakin University (AU)
- The University of Melbourne (AU)
- Venue
- The Journal of Physiology
- Publisher
- Wiley
- Published
- 2009-12-15
- Volume
- 587
- Issue
- 24
- Pages
- 5951-5958
- ISSN
- 0022-3751 (ISSN-L)
- 1469-7793
- PMC
- PMC2808551
- OpenAlex
- W1597446425
- Cited by
- 296
- References
- 28
- Citations by year
- 2026: 18 · 2025: 20 · 2024: 15 · 2023: 12 · 2022: 21 · 2021: 14 · 2020: 14 · 2019: 23 · 2018: 18 · 2017: 26 · 2016: 19 · 2015: 19 · 2014: 14 · 2013: 21 · 2012: 11
- FWCI
- 5.46
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Physiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Victoria University Research Repository (Victoria University) (submittedVersion)
- Funders
- National Health and Medical Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Keywords
- physical activity, skeletal muscle, histone modifications, histone acetylation, histone deacetylase, class IIa HDACs, HDAC4, HDAC5, nuclear export, chromatin remodeling, AMPK, CaMKII, transcriptional regulation, gene expression, cycling
- MeSH terms
- Adaptation, Physiological, Physical Exertion, Histones, Humans, Male, Muscle Contraction, Exercise, Muscle, Skeletal, Young Adult
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