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Human Skeletal Muscle Possesses an Epigenetic Memory of Hypertrophy

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Abstract

It is unknown if adult human skeletal muscle has an epigenetic memory of earlier encounters with growth. We report, for the first time in humans, genome-wide DNA methylation (850,000?CpGs) and gene expression analysis after muscle hypertrophy (loading), return of muscle mass to baseline (unloading), followed by later hypertrophy (reloading). We discovered increased frequency of hypomethylation across the genome after reloading (18,816?CpGs) versus earlier loading (9,153?CpG sites). We also identified AXIN1, GRIK2, CAMK4, TRAF1 as hypomethylated genes with enhanced expression after loading that maintained their hypomethylated status even during unloading where muscle mass returned to control levels, indicating a memory of these genes methylation signatures following earlier hypertrophy. Further, UBR5, RPL35a, HEG1, PLA2G16, SETD3 displayed hypomethylation and enhanced gene expression following loading, and demonstrated the largest increases in hypomethylation, gene expression and muscle mass after later reloading, indicating an epigenetic memory in these genes. Finally, genes; GRIK2, TRAF1, BICC1, STAG1 were epigenetically sensitive to acute exercise demonstrating hypomethylation after a single bout of resistance exercise that was maintained 22 weeks later with the largest increase in gene expression and muscle mass after reloading. Overall, we identify an important epigenetic role for a number of largely unstudied genes in muscle hypertrophy/memory.

Citation

(2018). Human Skeletal Muscle Possesses an Epigenetic Memory of Hypertrophy. Scientific reports, 8:1898 - 8:1898. https://doi.org/10.1038/s41598-018-20287-3

Acceptance Date Jan 16, 2018
Publication Date Jan 30, 2018
Journal Scientific Reports
Print ISSN 2045-2322
Publisher Nature Publishing Group
Pages 8:1898 - 8:1898
DOI https://doi.org/10.1038/s41598-018-20287-3
Keywords DNA methylation; Physiology
Publisher URL https://www.nature.com/articles/s41598-018-20287-3

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