Human Skeletal Muscle Possesses an Epigenetic Memory of Hypertrophy
Robert A. Seaborne,Robert A. Seaborne,Juliette A. Strauss,Matthew Cocks,Sam O. Shepherd,Thomas D. O'Brien,Ken A. van Someren,Phillip G. Bell,Chris Murgatroyd,James P. Morton,Claire E. Stewart,Adam P. Sharples,Adam P. Sharples +12 more
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TLDR
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.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.read more
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SETD3 is an actin histidine methyltransferase that prevents primary dystocia
Alex W. Wilkinson,Jonathan Diep,Shaobo Dai,Shuo Liu,Yaw Shin Ooi,Dan Song,Tie-Mei Li,John R. Horton,Xing Zhang,Chao Liu,Darshan V. Trivedi,Katherine M. Ruppel,Jose G. Vilches-Moure,Kerriann M. Casey,Justin Mak,Tina M. Cowan,Joshua E. Elias,Claude M. Nagamine,James A. Spudich,Xiaodong Cheng,Jan E. Carette,Or Gozani +21 more
TL;DR: SETD3 methylates mammalian actin at His73, and SETD3 deficiency impairs stimulus-induced contraction in primary human uterine smooth muscle cells and leads to maternal dystocia in mice, which supports the broader hypothesis that protein histidine methylation acts as a common regulatory mechanism.
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High-Intensity Exercise and Mitochondrial Biogenesis: Current Controversies and Future Research Directions
David Bishop,David Bishop,Javier Botella,Amanda J Genders,Matthew J. C. Lee,Nicholas J. Saner,Jujiao Kuang,Xu Yan,Cesare Granata +8 more
TL;DR: Current controversies in the field of mitochondrial biogenesis are examined to highlight some important methodological issues that need to be addressed to resolve existing conflicts.
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Antioxidant and Adaptative Response Mediated by Nrf2 during Physical Exercise
Nancy Vargas-Mendoza,Ángel Morales-González,Eduardo Madrigal-Santillán,Eduardo Madrigal-Bujaidar,Isela Álvarez-González,Luis Fernando Garcia-Melo,Liliana Anguiano-Robledo,Tomás Fregoso-Aguilar,José A. Morales-González +8 more
TL;DR: A review on the evidence that shows the effect different modalities of physical exercise exert on the antioxidant metabolic response directed by Nrf2, a powerful nuclear transcription factor that coordinates an antioxidant cytoprotector system complex stimulated by the increase in inoxidative stress.
Journal ArticleDOI
Comparative Transcriptome and Methylome Analysis in Human Skeletal Muscle Anabolism, Hypertrophy and Epigenetic Memory
Daniel C. Turner,Daniel C. Turner,Robert A. Seaborne,Robert A. Seaborne,Robert A. Seaborne,Adam P. Sharples,Adam P. Sharples +6 more
TL;DR: For the first time across the transcriptome and epigenome combined, this study identifies novel differentially methylated genes associated with human skeletal muscle anabolism, hypertrophy and epigenetic memory.
Journal ArticleDOI
Epigenetic changes in healthy human skeletal muscle following exercise: a systematic review
Macsue Jacques,Danielle Hiam,Jeffrey M. Craig,Jeffrey M. Craig,Romain Barrès,Nir Eynon,Sarah Voisin +6 more
TL;DR: Several epigenetic markers including DNA methylation of genes known to be differentially expressed after exercise and myomiRs were reported to be modified after exercise, with potential influence on skeletal muscle metabolism.
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