The 24-Hour Time Course of Integrated Molecular Responses to Resistance Exercise in Human Skeletal Muscle Implicates MYC as a Hypertrophic Regulator That is Sufficient for Growth

S. Edman, 3rd Jones R. G., P. R. Jannig, R. Fernandez-Gonzalo, J. Norrbom, N. T. Thomas, S. Khadgi, P. J. Koopmans, F. Morena, C. S. Peterson, L. N. Scott, N. P. Greene, V. C. Figueiredo, C. S. Fry, L. Zhengye, J. T. Lanner, Y. Wen, B. Alkner, K. A. Murach, F. von Walden

Research output: Contribution to journalArticlepeer-review

Abstract

Molecular control of recovery after exercise in muscle is temporally dynamic. A time course of biopsies around resistance exercise (RE) combined with -omics is necessary to better comprehend the molecular contributions of skeletal muscle adaptation in humans. Vastus lateralis biopsies before and 30 minutes, 3-, 8-, and 24-hours after acute RE were collected. A time-point matched biopsy-only group was also included. RNA-sequencing defined the transcriptome while DNA methylomics and computational approaches complemented these data. The post-RE time course revealed: 1) DNA methylome responses at 30 minutes corresponded to upregulated genes at 3 hours, 2) a burst of translation- and transcription-initiation factor-coding transcripts occurred between 3 and 8 hours, 3) global gene expression peaked at 8 hours, 4) ribosome-related genes dominated the mRNA landscape between 8 and 24 hours, 5) methylation-regulated MYC was a highly influential transcription factor throughout the 24-hour recovery and played a primary role in ribosome-related mRNA levels between 8 and 24 hours. The influence of MYC in human muscle adaptation was strengthened by transcriptome information from acute MYC overexpression in mouse muscle. To test whether MYC was sufficient for hypertrophy, we generated a muscle fiber-specific doxycycline inducible model of pulsatile MYC induction. Periodic 48-hour pulses of MYC over 4 weeks resulted in higher muscle mass and fiber size in the soleus of adult female mice. Collectively, we present a temporally resolved resource for understanding molecular adaptations to RE in muscle and reveal MYC as a regulator of RE-induced mRNA levels and hypertrophy.
Original languageAmerican English
JournalbioRxiv
DOIs
StatePublished - 2024

Bibliographical note

Edman, Sebastian Jones, Ronald G 3rd Jannig, Paulo R Fernandez-Gonzalo, Rodrigo Norrbom, Jessica Thomas, Nicholas T Khadgi, Sabin Koopmans, Pieter Jan Morena, Francielly Peterson, Calvin S Scott, Logan N Greene, Nicholas P Figueiredo, Vandre C Fry, Christopher S Zhengye, Liu Lanner, Johanna T Wen, Yuan Alkner, Bjorn Murach, Kevin A von Walden, Ferdinand eng K99 AR081367/AR/NIAMS NIH HHS/ P20 GM139768/GM/NIGMS NIH HHS/ R01 AG080047/AG/NIA NIH HHS/ Preprint 2024/04/08 bioRxiv [Preprint]. 2024 Mar 27:2024.03.26.586857. doi: 10.1101/2024.03.26.586857.

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