Coordinated Regulation of Myonuclear DNA Methylation, mRNA, and miRNA Levels Associates With the Metabolic Response to Rapid Synergist Ablation-Induced Skeletal Muscle Hypertrophy in Female Mice

Ahmed Ismaeel, Nicholas T. Thomas, Mariah McCashland, Ivan J. Vechetti, Sebastian Edman, Johanna T. Lanner, Vandré C. Figueiredo, Christopher S. Fry, John McCarthy, Yuan Wen, Kevin A. Murach, Ferdinand von Walden

Research output: Contribution to journalArticlepeer-review

Abstract

The central dogma of molecular biology dictates the general flow of molecular information from DNA that leads to a functional cellular outcome. In skeletal muscle fibers, the extent to which global myonuclear transcriptional alterations, accounting for epigenetic and post-transcriptional influences, contribute to an adaptive stress response is not clearly defined. In this investigation, we leveraged an integrated analysis of the myonucleus-specific DNA methylome and transcriptome, as well as myonuclear small RNA profiling to molecularly define the early phase of skeletal muscle fiber hypertrophy. The analysis of myonucleus-specific mature microRNA and other small RNA species provides new directions for exploring muscle adaptation and complemented the methylation and transcriptional information. Our integrated multi-omics interrogation revealed a coordinated myonuclear molecular landscape during muscle loading that coincides with an acute and rapid reduction of oxidative metabolism. This response may favor a biosynthesis-oriented metabolic program that supports rapid hypertrophic growth.

Original languageEnglish
Article numberzqad062
JournalFunction
Volume5
Issue number1
DOIs
StatePublished - 2024

Bibliographical note

Publisher Copyright:
© 2024 Oxford University Press. All rights reserved.

Keywords

  • epigenetics
  • mitochondrial respiration
  • oxidative metabolism
  • RNA sequencing
  • RRBS
  • small RNA sequencing

ASJC Scopus subject areas

  • Physiology
  • Molecular Medicine
  • Cell Biology
  • Cancer Research

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