| Autor: |
Edman, Sebastian, Jones III, Ronald G, Jannig, Paulo R, Fernandez-Gonzalo, Rodrigo, Norrbom, Jessica, Thomas, Nicholas T, Khadgi, Sabin, Koopmans, Pieter J, Morena, Francielly, Chambers, Toby L, Peterson, Calvin S, Scott, Logan N, Greene, Nicholas P, Figueiredo, Vandre C, Fry, Christopher S, Zhengye, Liu, Lanner, Johanna T, Wen, Yuan, Alkner, Björn, Murach, Kevin A |
| Zdroj: |
EMBO Reports; Dec2024, Vol. 25 Issue 12, p5810-5837, 28p |
| Abstrakt: |
A detailed understanding of molecular responses to a hypertrophic stimulus in skeletal muscle leads to therapeutic advances aimed at promoting muscle mass. To decode the molecular factors regulating skeletal muscle mass, we utilized a 24-h time course of human muscle biopsies after a bout of resistance exercise. Our findings indicate: (1) the DNA methylome response at 30 min corresponds to upregulated genes at 3 h, (2) a burst of translation- and transcription-initiation factor-coding transcripts occurs between 3 and 8 h, (3) changes to global protein-coding gene expression peaks at 8 h, (4) ribosome-related genes dominate the mRNA landscape between 8 and 24 h, (5) methylation-regulated MYC is a highly influential transcription factor throughout recovery. To test whether MYC is sufficient for hypertrophy, we periodically pulse MYC in skeletal muscle over 4 weeks. Transient MYC increases muscle mass and fiber size in the soleus of adult mice. We present a temporally resolved resource for understanding molecular adaptations to resistance exercise in muscle (http://data.myoanalytics.com) and suggest that controlled MYC doses influence the exercise-related hypertrophic transcriptional landscape. Synopsis: A 24-h time course of recovery after an acute hypertrophic stimulus—resistance exercise—unravels the temporal dynamics of gene expression in healthy untrained human skeletal muscle. MYC's pulsatile pattern after exercise likely facilitates its hypertrophic function in differentiated adult muscle cells. Global protein-coding gene expression changes peak at 8 h after an acute hypertrophic stimulus in human skeletal muscle, and early DNA methylation responses predict later gene expression changes. MYC is a key transcription factor regulating gene expression after resistance exercise, specifically during late recovery (8–24 h). Genetically controlled pulses of Myc in skeletal muscle of mice are sufficient for hypertrophy. A 24-h time course of recovery after an acute hypertrophic stimulus—resistance exercise—unravels the temporal dynamics of gene expression in human skeletal muscle. MYC's pulsatile pattern after exercise likely facilitates its hypertrophic function in differentiated adult muscle cells. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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