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    Exercise-associated DNA methylation change in skeletal muscle and the importance of imprinted genes: a bioinformatics meta-analysis

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    Authors
    Brown, William Michael
    Affiliation
    University of Bedfordshire
    Issue Date
    2015-03-30
    Subjects
    C400 Genetics
    C420 Human Genetics
    C431 Medical Genetics
    C440 Molecular Genetics
    C182 Evolution
    C600 Sports Science
    C120 Behavioural Biology
    bioinformatics
    DNA methylation
    excercise
    
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    Abstract
    BACKGROUND: 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.
    Citation
    Brown, 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.
    Publisher
    BMJ Publishing Group Limited
    Journal
    British Journal of Sports Medicine
    URI
    http://hdl.handle.net/10547/552912
    DOI
    10.1136/bjsports-2014-094073
    PubMed ID
    25824446
    Additional Links
    https://bjsm.bmj.com/content/49/24/1567.info
    Type
    Article
    Language
    en
    Description
    Using 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/
    ISSN
    1473-0480
    Sponsors
    European Office of Aerospace Research & Development
    ae974a485f413a2113503eed53cd6c53
    10.1136/bjsports-2014-094073
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    Muscle Cellular and Molecular Physiology

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