title: Myonuclear transcription is responsive to mechanical load and DNA content but uncoupled from cell size during hypertrophy.
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 μm(2)) 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.
authors.affiliation: Department of Physiology, College of Medicine, University of Kentucky, Lexington, KT 40536 Center for Muscle Biology, University of Kentucky, Lexington, KT 40536.
authors.forename: Tyler J
authors.initials: TJ
authors.lastname: Kirby
authors.affiliation: Department of Physiology, College of Medicine, University of Kentucky, Lexington, KT 40536.
authors.forename: Rooshil M
authors.initials: RM
authors.lastname: Patel
authors.affiliation: Department of Physiology, College of Medicine, University of Kentucky, Lexington, KT 40536.
authors.forename: Timothy S
authors.initials: TS
authors.lastname: McClintock
authors.affiliation: Center for Muscle Biology, University of Kentucky, Lexington, KT 40536 Department of Rehabilitation Sciences, College of Health Sciences, University of Kentucky, Lexington, KT 40536.
authors.forename: Esther E
authors.initials: EE
authors.lastname: Dupont-Versteegden
authors.affiliation: Center for Muscle Biology, University of Kentucky, Lexington, KT 40536 Department of Rehabilitation Sciences, College of Health Sciences, University of Kentucky, Lexington, KT 40536.
authors.forename: Charlotte A
authors.initials: CA
authors.lastname: Peterson
authors.affiliation: Department of Physiology, College of Medicine, University of Kentucky, Lexington, KT 40536 Center for Muscle Biology, University of Kentucky, Lexington, KT 40536 jjmcca2@email.uky.edu.
authors.forename: John J
authors.initials: JJ
authors.lastname: McCarthy
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D048429:Cell Size; D004247:DNA / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006984:Hypertrophy / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D018485:Muscle Fibers, Skeletal / Q000473:pathology* / Q000502:physiology; D018482:Muscle, Skeletal / Q000473:pathology; D012323:RNA Processing, Post-Transcriptional; D014158:Transcription, Genetic
chemical_list: D004247:DNA