Epigenetic rewiring of skeletal muscle enhancers after exercise training supports a role in whole-body function and human health
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 hum...
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doaj-a43dd0005ef848409fc736494902259e2021-08-08T04:18:06ZengElsevierMolecular Metabolism2212-87782021-11-0153101290Epigenetic rewiring of skeletal muscle enhancers after exercise training supports a role in whole-body function and human healthKristine Williams0Germán D. Carrasquilla1Lars Roed Ingerslev2Mette Yde Hochreuter3Svenja Hansson4Nicolas J. Pillon5Ida Donkin6Soetkin Versteyhe7Juleen R. Zierath8Tuomas O. Kilpeläinen9Romain Barrès10Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen N, DenmarkNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen N, DenmarkNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen N, DenmarkNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen N, DenmarkNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen N, DenmarkDepartment of Physiology and Pharmacology, Karolinska Institutet, 171 77, Stockholm, SwedenNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen N, DenmarkNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen N, DenmarkNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen N, Denmark; Department of Physiology and Pharmacology, Karolinska Institutet, 171 77, Stockholm, Sweden; Department of Molecular Medicine and Surgery, Karolinska University Hospital, 171 76, Stockholm, SwedenNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen N, DenmarkNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen N, Denmark; Corresponding author. Mærsk Tower 7.7, Blegdamsvej 3B, 2200, Copenhagen N, Denmark. Tel. +45 35 33 72 88.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.http://www.sciencedirect.com/science/article/pii/S2212877821001356ExerciseSkeletal muscleEnhancersGWASHistone |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 |
spellingShingle |
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 Epigenetic rewiring of skeletal muscle enhancers after exercise training supports a role in whole-body function and human health Molecular Metabolism Exercise Skeletal muscle Enhancers GWAS Histone |
author_facet |
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 |
author_sort |
Kristine Williams |
title |
Epigenetic rewiring of skeletal muscle enhancers after exercise training supports a role in whole-body function and human health |
title_short |
Epigenetic rewiring of skeletal muscle enhancers after exercise training supports a role in whole-body function and human health |
title_full |
Epigenetic rewiring of skeletal muscle enhancers after exercise training supports a role in whole-body function and human health |
title_fullStr |
Epigenetic rewiring of skeletal muscle enhancers after exercise training supports a role in whole-body function and human health |
title_full_unstemmed |
Epigenetic rewiring of skeletal muscle enhancers after exercise training supports a role in whole-body function and human health |
title_sort |
epigenetic rewiring of skeletal muscle enhancers after exercise training supports a role in whole-body function and human health |
publisher |
Elsevier |
series |
Molecular Metabolism |
issn |
2212-8778 |
publishDate |
2021-11-01 |
description |
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. |
topic |
Exercise Skeletal muscle Enhancers GWAS Histone |
url |
http://www.sciencedirect.com/science/article/pii/S2212877821001356 |
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