Epigenetic rewiring of skeletal muscle enhancers after exercise training supports a role in the whole-body function and human health

Kristine Williams; Germán D Carrasquilla; Lars Roed Ingerslev; Mette Yde Hochreuter; Svenja Hansson; Nicolas J Pillon; Ida Donkin; Soetkin Versteyhe; Juleen R Zierath; Tuomas O. Kilpeläinen; Romain Barrès

doi:10.1016/j.molmet.2021.101290

Epigenetic rewiring of skeletal muscle enhancers after exercise training supports a role in the whole-body function and human health

Kristine Williams, Germán D Carrasquilla, Lars Roed Ingerslev, Mette Yde Hochreuter, Svenja Hansson, Nicolas J Pillon, Ida Donkin, Soetkin Versteyhe, Juleen R Zierath, Tuomas O. Kilpeläinen, Romain Barrès^*

^*Corresponding author for this work

Research output: Contribution to journal › Journal article › Research › peer-review

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Abstract

OBJECTIVES: Regular physical exercise improves health by reducing the risk of a plethora of chronic disorders. We hypothesized that endurance exercise training remodels the activity of gene enhancers in skeletal muscle and that this remodeling contributes to the beneficial effects of exercise on human health.

METHODS AND RESULTS: By studying changes in histone modifications, we mapped the genome-wide positions and activities of enhancers in skeletal muscle biopsies collected from young sedentary men before and after 6 weeks of endurance exercise. We identified extensive remodeling of enhancer activities after exercise training, with a large subset of the remodeled enhancers located in the proximity of genes transcriptionally regulated after exercise. By overlapping the position of enhancers with genetic variants, we identified an enrichment of disease-associated genetic variants within the exercise-remodeled enhancers.

CONCLUSION: Our data provide evidence of a functional link between epigenetic rewiring of enhancers to control their activity after exercise training and the modulation of disease risk in humans.

Original language	English
Article number	101290
Journal	Molecular Metabolism
Volume	53
Number of pages	13
ISSN	2212-8778
DOIs	https://doi.org/10.1016/j.molmet.2021.101290
Publication status	Published - 2021

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Epigenetic rewiring of skeletal muscle enhancers after exercise training supports a role in whole-body function and human healthFinal published version, 2.19 MBLicence: CC BY

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Williams, K., Carrasquilla, G. D., Ingerslev, L. R., Hochreuter, M. Y., Hansson, S., Pillon, N. J., Donkin, I., Versteyhe, S., Zierath, J. R., Kilpeläinen, T. O., & Barrès, R. (2021). Epigenetic rewiring of skeletal muscle enhancers after exercise training supports a role in the whole-body function and human health. Molecular Metabolism, 53, [101290]. https://doi.org/10.1016/j.molmet.2021.101290

Epigenetic rewiring of skeletal muscle enhancers after exercise training supports a role in the whole-body function and human health. / Williams, Kristine; Carrasquilla, Germán D ; Ingerslev, Lars Roed; Hochreuter, Mette Yde; Hansson, Svenja; Pillon, Nicolas J; Donkin, Ida; Versteyhe, Soetkin; Zierath, Juleen R ; Kilpeläinen, Tuomas O.; Barrès, Romain.

In: Molecular Metabolism, Vol. 53, 101290, 2021.

Research output: Contribution to journal › Journal article › Research › peer-review

Williams, K, Carrasquilla, GD , Ingerslev, LR, Hochreuter, MY, Hansson, S, Pillon, NJ, Donkin, I, Versteyhe, S, Zierath, JR , Kilpeläinen, TO & Barrès, R 2021, 'Epigenetic rewiring of skeletal muscle enhancers after exercise training supports a role in the whole-body function and human health', Molecular Metabolism, vol. 53, 101290. https://doi.org/10.1016/j.molmet.2021.101290

Williams, Kristine ; Carrasquilla, Germán D ; Ingerslev, Lars Roed ; Hochreuter, Mette Yde ; Hansson, Svenja ; Pillon, Nicolas J ; Donkin, Ida ; Versteyhe, Soetkin ; Zierath, Juleen R ; Kilpeläinen, Tuomas O. ; Barrès, Romain. / Epigenetic rewiring of skeletal muscle enhancers after exercise training supports a role in the whole-body function and human health. In: Molecular Metabolism. 2021 ; Vol. 53.

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abstract = "OBJECTIVES: Regular physical exercise improves health by reducing the risk of a plethora of chronic disorders. We hypothesized that endurance exercise training remodels the activity of gene enhancers in skeletal muscle and that this remodeling contributes to the beneficial effects of exercise on human health.METHODS AND RESULTS: By studying changes in histone modifications, we mapped the genome-wide positions and activities of enhancers in skeletal muscle biopsies collected from young sedentary men before and after 6 weeks of endurance exercise. We identified extensive remodeling of enhancer activities after exercise training, with a large subset of the remodeled enhancers located in the proximity of genes transcriptionally regulated after exercise. By overlapping the position of enhancers with genetic variants, we identified an enrichment of disease-associated genetic variants within the exercise-remodeled enhancers.CONCLUSION: Our data provide evidence of a functional link between epigenetic rewiring of enhancers to control their activity after exercise training and the modulation of disease risk in humans.",

author = "Kristine Williams and Carrasquilla, {Germ{\'a}n D} and Ingerslev, {Lars Roed} and Hochreuter, {Mette Yde} and Svenja Hansson and Pillon, {Nicolas J} and Ida Donkin and Soetkin Versteyhe and Zierath, {Juleen R} and Kilpel{\"a}inen, {Tuomas O.} and Romain Barr{\`e}s",

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AU - Hansson, Svenja

AU - Pillon, Nicolas J

AU - Donkin, Ida

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AU - Kilpeläinen, Tuomas O.

AU - Barrès, Romain

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AB - OBJECTIVES: Regular physical exercise improves health by reducing the risk of a plethora of chronic disorders. We hypothesized that endurance exercise training remodels the activity of gene enhancers in skeletal muscle and that this remodeling contributes to the beneficial effects of exercise on human health.METHODS AND RESULTS: By studying changes in histone modifications, we mapped the genome-wide positions and activities of enhancers in skeletal muscle biopsies collected from young sedentary men before and after 6 weeks of endurance exercise. We identified extensive remodeling of enhancer activities after exercise training, with a large subset of the remodeled enhancers located in the proximity of genes transcriptionally regulated after exercise. By overlapping the position of enhancers with genetic variants, we identified an enrichment of disease-associated genetic variants within the exercise-remodeled enhancers.CONCLUSION: Our data provide evidence of a functional link between epigenetic rewiring of enhancers to control their activity after exercise training and the modulation of disease risk in humans.

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