Methylome of human skeletal muscle after acute &amp; chronic resistance exercise training, detraining &amp; retraining

Seaborne, Robert A.; Strauss, Juliette A.; Cocks, Matt; Shepherd, Sam; O’Brien, Thomas D.; Someren, Ken A. van; Bell, Phillip G.; Murgatroyd, Chris; Morton, James P.; Stewart, Claire E.; Mein, Charles A.; Sharples, Adam P.

doi:10.1038/sdata.2018.213

Cited by 71 publications

(134 citation statements)

References 19 publications

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“…Importantly, the largest increases in hypomethylation, gene expression and muscle mass were observed after later reloading/retraining. Therefore, the level of UBR5 gene expression was positively and strongly correlated with the increases in lean leg mass during periods of training and retraining (Seaborne et al 2018b). These data indicated that UBR5 was an E3 ligase associated with muscle hypertrophy rather than muscle atrophy.…”

Section: Introductionmentioning

confidence: 79%

“…The full biopsy procedure and the primary cell isolation procedures have been described previously (Seaborne et al . ; Seaborne et al . ; Turner et al .…”

Section: Methodsmentioning

confidence: 99%

“…Bioengineered muscle constructs were then transferred to bioreactor chambers (TC-3; Ebers, Zaragoza, Spain) ( Fig. 4Ba) for subsequent loading, which involved 5 exercises × 4 (Seaborne et al 2018b) after an initial period of resistance exercise-induced hypertrophy (loading), followed by exercise cessation (unloading) where muscle mass returned to baseline levels, and a later period of resistance exercise-induced hypertrophy (reloading). Ba, top left: representative macroscopic image of c2c12 bioengineered skeletal muscle used as a model to assess the response of UBR5 to acute loading.…”

Section: Mechanical Loading Of Bioengineered Skeletal Muscle In Vitromentioning

confidence: 99%

“…However, HECT domain E3 ligases remain relatively unstudied in skeletal muscle atrophy or remodelling. Interestingly, we have recently demonstrated that a HECT domain E3 ligase called UBR5 (also known as EDD1), previously uncharacterized in skeletal muscle, is an epigenetically regulated gene (identified using 850,000 DNA methylation arrays) hypomethylated after resistance exercise-induced muscle hypertrophy in humans (termed loading/training) (Seaborne et al 2018b). In the previous study, resistance exercise-induced hypertrophy was followed by complete cessation of exercise and a return of lean leg mass to pre-exercise baseline levels (unloading/detraining).…”

Section: Introductionmentioning

confidence: 99%

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UBR5 is a novel E3 ubiquitin ligase involved in skeletal muscle hypertrophy and recovery from atrophy

Seaborne

Hughes

Turner

et al. 2019

The Journal of Physiology

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Key points We have recently identified that a HECT domain E3 ubiquitin ligase, named UBR5, is altered epigenetically (via DNA methylation) after human skeletal muscle hypertrophy, where its gene expression is positively correlated with increasing lean leg mass after training and retraining. In the present study we extensively investigate this novel and uncharacterised E3 ubiquitin ligase (UBR5) in skeletal muscle atrophy, recovery from atrophy and injury, anabolism and hypertrophy. We demonstrated that UBR5 was epigenetically altered via DNA methylation during recovery from atrophy. We also determined that UBR5 was alternatively regulated versus well characterised E3 ligases, MuRF1/MAFbx, at the gene expression level during atrophy, recovery from atrophy and hypertrophy. UBR5 also increased at the protein level during recovery from atrophy and injury, hypertrophy and during human muscle cell differentiation. Finally, in humans, genetic variations of the UBR5 gene were strongly associated with larger fast‐twitch muscle fibres and strength/power performance versus endurance/untrained phenotypes. Abstract We aimed to investigate a novel and uncharacterized E3 ubiquitin ligase in skeletal muscle atrophy, recovery from atrophy/injury, anabolism and hypertrophy. We demonstrated an alternate gene expression profile for UBR5 vs. well characterized E3‐ligases, MuRF1/MAFbx, where, after atrophy evoked by continuous‐low‐frequency electrical‐stimulation in rats, MuRF1/MAFbx were both elevated, yet UBR5 was unchanged. Furthermore, after recovery of muscle mass post TTX‐induced atrophy in rats, UBR5 was hypomethylated and increased at the gene expression level, whereas a suppression of MuRF1/MAFbx was observed. At the protein level, we also demonstrated a significant increase in UBR5 after recovery of muscle mass from hindlimb unloading in both adult and aged rats, as well as after recovery from atrophy evoked by nerve crush injury in mice. During anabolism and hypertrophy, UBR5 gene expression increased following acute loading in three‐dimensional bioengineered mouse muscle in vitro, and after chronic electrical stimulation‐induced hypertrophy in rats in vivo, without increases in MuRF1/MAFbx. Additionally, UBR5 protein abundance increased following functional overload‐induced hypertrophy of the plantaris muscle in mice and during differentiation of primary human muscle cells. Finally, in humans, genetic association studies (>700,000 single nucleotide polymorphisms) demonstrated that the A alleles of rs10505025 and rs4734621 single nucleotide polymorphisms in the UBR5 gene were strongly associated with larger cross‐sectional area of fast‐twitch muscle fibres and favoured strength/power vs. endurance/untrained phenotypes. Overall, we suggest that: (i) UBR5 comprises a novel E3 ubiquitin ligase that is inversely regulated to MuRF1/MAFbx; (ii) UBR5 is epigenetically regulated; and (iii) UBR5 is elevated at both the gene expression and protein level during recovery from skeletal muscle atrophy and hypertrophy.

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Section: Introductionmentioning

confidence: 79%

“…The full biopsy procedure and the primary cell isolation procedures have been described previously (Seaborne et al . ; Seaborne et al . ; Turner et al .…”

Section: Methodsmentioning

confidence: 99%

Section: Mechanical Loading Of Bioengineered Skeletal Muscle In Vitromentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

UBR5 is a novel E3 ubiquitin ligase involved in skeletal muscle hypertrophy and recovery from atrophy

Seaborne

Hughes

Turner

et al. 2019

The Journal of Physiology

Self Cite

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“…Recently, a previously uncharacterized HECT domain E3 ligase called UBR5 (or EDD1) was found to be hypomethylated after resistance exercise‐induced hypertrophy in humans (Seaborne et al . , b ). In this study, the methylation profile of UBR5 appeared to be inversely correlated with changes in UBR5 gene expression, and the expression of UBR5 was positively correlated with the gains in lean leg mass during training and retraining.…”

mentioning

confidence: 99%

The role of the recently discovered E3 ubiquitin ligase UBR5 in skeletal muscle mass regulation

Dablainville

Sanchez

2019

The Journal of Physiology

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Mechanical loading of bioengineered skeletal muscle in vitro recapitulates gene expression signatures of resistance exercise in vivo

Turner

Gorski

Seaborne

et al. 2021

Journal Cellular Physiology

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Understanding the role of mechanical loading and exercise in skeletal muscle (SkM) is paramount for delineating the molecular mechanisms that govern changes in muscle mass. However, it is unknown whether loading of bioengineered SkM in vitro adequately recapitulates the molecular responses observed after resistance exercise (RE) in vivo. To address this, the transcriptional and epigenetic (DNA methylation) responses were compared after mechanical loading in bioengineered SkM in vitro and after RE in vivo. Specifically, genes known to be upregulated/hypomethylated after RE in humans were analyzed. Ninety-three percent of these genes demonstrated similar changes in gene expression post-loading in the bioengineered muscle when compared to acute RE in humans. Furthermore, similar differences in gene expression were observed between loaded bioengineered SkM and after programmed RT in rat SkM tissue. Hypomethylation occurred for only one of the genes analysed (GRIK2) post-loading in bioengineered SkM. To further validate these findings, DNA methylation and mRNA expression of known hypomethylated and upregulated genes post-acute RE in humans were also analyzed at 0.5, 3, and 24 h post-loading in bioengineered muscle. The largest changes in gene expression occurred at 3 h, whereby 82% and 91% of genes responded similarly whenThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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Methylome of human skeletal muscle after acute & chronic resistance exercise training, detraining & retraining

Cited by 71 publications

References 19 publications

UBR5 is a novel E3 ubiquitin ligase involved in skeletal muscle hypertrophy and recovery from atrophy

UBR5 is a novel E3 ubiquitin ligase involved in skeletal muscle hypertrophy and recovery from atrophy

The role of the recently discovered E3 ubiquitin ligase UBR5 in skeletal muscle mass regulation

Mechanical loading of bioengineered skeletal muscle in vitro recapitulates gene expression signatures of resistance exercise in vivo

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