Exercise-associated DNA methylation change in skeletal muscle and the importance of imprinted genes: a bioinformatics meta-analysis
AuthorsBrown, William Michael
AffiliationUniversity of Bedfordshire
C420 Human Genetics
C431 Medical Genetics
C440 Molecular Genetics
C600 Sports Science
C120 Behavioural Biology
MetadataShow full item record
AbstractBACKGROUND: Epigenetics is the study of processes-beyond DNA sequence alteration-producing heritable characteristics. For example, DNA methylation modifies gene expression without altering the nucleotide sequence. A well-studied DNA methylation-based phenomenon is genomic imprinting (ie, genotype-independent parent-of-origin effects). OBJECTIVE: We aimed to elucidate: (1) the effect of exercise on DNA methylation and (2) the role of imprinted genes in skeletal muscle gene networks (ie, gene group functional profiling analyses). DESIGN: Gene ontology (ie, gene product elucidation)/meta-analysis. DATA SOURCES: 26 skeletal muscle and 86 imprinted genes were subjected to g:Profiler ontology analysis. Meta-analysis assessed exercise-associated DNA methylation change. DATA EXTRACTION: g:Profiler found four muscle gene networks with imprinted loci. Meta-analysis identified 16 articles (387 genes/1580 individuals) associated with exercise. Age, method, sample size, sex and tissue variation could elevate effect size bias. DATA SYNTHESIS: Only skeletal muscle gene networks including imprinted genes were reported. Exercise-associated effect sizes were calculated by gene. Age, method, sample size, sex and tissue variation were moderators. RESULTS: Six imprinted loci (RB1, MEG3, UBE3A, PLAGL1, SGCE, INS) were important for muscle gene networks, while meta-analysis uncovered five exercise-associated imprinted loci (KCNQ1, MEG3, GRB10, L3MBTL1, PLAGL1). DNA methylation decreased with exercise (60% of loci). Exercise-associated DNA methylation change was stronger among older people (ie, age accounted for 30% of the variation). Among older people, genes exhibiting DNA methylation decreases were part of a microRNA-regulated gene network functioning to suppress cancer. CONCLUSIONS: Imprinted genes were identified in skeletal muscle gene networks and exercise-associated DNA methylation change. Exercise-associated DNA methylation modification could rewind the 'epigenetic clock' as we age. TRIAL REGISTRATION NUMBER: CRD42014009800.
CitationBrown, William M. (2015) 'Exercise-associated DNA methylation change in skeletal muscle and the importance of imprinted genes: a bioinformatics meta-analysis', British Journal of Sports Medicine, 49, pp.1567-1578.
PublisherBMJ Publishing Group Limited
DescriptionUsing bioinformatics and meta-analytic tools, Dr Brown reveals that imprinted genes are involved in skeletal muscle gene networks and exercise-associated DNA methylation change. Brown finds that exercise-associated DNA methylation is stronger in older (compared to younger) individuals and may rewind the epigenetic clock. Numerous mediators were found that could affect the degree of exercise-associated DNA methylation change such as experimental design, sample size, gender, tissue and exercise type. A list of epigenetic candidate loci are developed that could help future researchers understand how exercise may activate tumour suppressor genes and deactivate growth loci amongst older individuals. Brown refers to this as an epigenetic adaptive response to antagonistic pleiotropy (i.e., when genes with multiple targets are beneficial at younger, but not older ages after selection has weakened). For further discussion of the findings see Dr Brown's blog https://sociogenomics.wordpress.com/2015/04/12/genomic-imprinting-human-skeletal-muscle-and-exercise-epigenetics/
SponsorsEuropean Office of Aerospace Research & Development
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