Acute exercise remodels promoter methylation in human skeletal muscle

Romain Barrès; Jie Yan; Brendan Egan; Jonas Thue Treebak; Morten Rasmussen; Tomas Fritz; Kenneth Caidahl; Anna Krook; Donal J O'Gorman; Juleen R Zierath

doi:10.1016/j.cmet.2012.01.001

Acute exercise remodels promoter methylation in human skeletal muscle

Romain Barrès, Jie Yan, Brendan Egan, Jonas Thue Treebak, Morten Rasmussen, Tomas Fritz, Kenneth Caidahl, Anna Krook, Donal J O'Gorman, Juleen R Zierath

502 Citationer (Scopus)

Abstract

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.

Originalsprog	Engelsk
Tidsskrift	Cell Metabolism
Vol/bind	15
Udgave nummer	3
Sider (fra-til)	405-11
Antal sider	7
ISSN	1550-4131
DOI	https://doi.org/10.1016/j.cmet.2012.01.001
Status	Udgivet - 7 mar. 2012

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10.1016/j.cmet.2012.01.001

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title = "Acute exercise remodels promoter methylation in human skeletal muscle",

abstract = "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.",

keywords = "Adult, Animals, DNA Methylation, Exercise, Female, Humans, Male, Mice, Mice, Inbred C57BL, Muscle, Skeletal, Young Adult",

author = "Romain Barr{\`e}s and Jie Yan and Brendan Egan and Treebak, {Jonas Thue} and Morten Rasmussen and Tomas Fritz and Kenneth Caidahl and Anna Krook and O'Gorman, {Donal J} and Zierath, {Juleen R}",

year = "2012",

month = mar,

day = "7",

doi = "10.1016/j.cmet.2012.01.001",

language = "English",

volume = "15",

pages = "405--11",

journal = "Cell Metabolism",

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TY - JOUR

T1 - Acute exercise remodels promoter methylation in human skeletal muscle

AU - Barrès, Romain

AU - Yan, Jie

AU - Egan, Brendan

AU - Treebak, Jonas Thue

AU - Rasmussen, Morten

AU - Fritz, Tomas

AU - Caidahl, Kenneth

AU - Krook, Anna

AU - O'Gorman, Donal J

AU - Zierath, Juleen R

PY - 2012/3/7

Y1 - 2012/3/7

N2 - 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.

AB - 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.

KW - Adult

KW - Animals

KW - DNA Methylation

KW - Exercise

KW - Female

KW - Humans

KW - Male

KW - Mice

KW - Mice, Inbred C57BL

KW - Muscle, Skeletal

KW - Young Adult

U2 - 10.1016/j.cmet.2012.01.001

DO - 10.1016/j.cmet.2012.01.001

M3 - Journal article

C2 - 22405075

SN - 1550-4131

VL - 15

SP - 405

EP - 411

JO - Cell Metabolism

JF - Cell Metabolism

IS - 3

ER -

Acute exercise remodels promoter methylation in human skeletal muscle

Abstract

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