Myonuclear transcription is responsive to mechanical load and DNA content but uncoupled from cell size during hypertrophy

Tyler J. Kirby, Rooshil M. Patel, Timothy S. McClintock, Esther E. Dupont-Versteegden, Charlotte A. Peterson, John J. McCarthy

Research output: Contribution to journalArticlepeer-review

57 Scopus citations

Abstract

Myofibers increase size and DNA content in response to a hypertrophic stimulus, thus providing a physiological model with which to study how these factors affect global transcription. Using 5-ethynyl uridine (EU) to metabolically label nascent RNA, we measured a sevenfold increase in myofiber transcription during early hypertrophy before a change in cell size and DNA content. The typical increase in myofiber DNA content observed at the later stage of hypertrophy was associated with a significant decrease in the percentage of EU-positive myonuclei; however, when DNA content was held constant by preventing myonuclear accretion via satellite cell depletion, both the number of transcriptionally active myonuclei and the amount of RNA generated by each myonucleus increased. During late hypertrophy, transcription did not scale with cell size, as smaller myofibers (<1000 μm2) demonstrated the highest transcriptional activity. Finally, transcription was primarily responsible for changes in the expression of genes known to regulate myofiber size. These findings show that resident myonuclei possess a significant reserve capacity to up-regulate transcription during hypertrophy and that myofiber transcription is responsive to DNA content but uncoupled from cell size during hypertrophy.

Original languageEnglish
Pages (from-to)788-798
Number of pages11
JournalMolecular Biology of the Cell
Volume27
Issue number5
DOIs
StatePublished - Mar 1 2016

Bibliographical note

Funding Information:
We thank Chris Fry for helping with tissue collection and Sarah White for statistical advice. We also thank Sami Michaelis for helping with image analysis. This work was supported by National Institutes of Health Grant AR060701 to J.J.M. and C.A.P.

Publisher Copyright:
© 2016 Kirby et al.

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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