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IIb or not IIb? Regulation of myosin heavy chain gene expression in mice and men

Authors
  • Harrison, Brooke C1
  • Allen, David L2
  • Leinwand, Leslie A1
  • 1 Cellular and Developmental Biology University of Colorado at Boulder, Department of Molecular, Boulder, 80309, USA , Boulder (United States)
  • 2 University of Colorado at Boulder, Department of Integrative Physiology, Boulder, 80309, USA , Boulder (United States)
Type
Published Article
Journal
Skeletal Muscle
Publisher
Springer (Biomed Central Ltd.)
Publication Date
Feb 01, 2011
Volume
1
Issue
1
Identifiers
DOI: 10.1186/2044-5040-1-5
Source
Springer Nature
Keywords
License
Yellow

Abstract

BackgroundWhile the myosin heavy chain IIb isoform (MyHC-IIb) is the predominant motor protein in most skeletal muscles of rats and mice, the messenger RNA (mRNA) for this isoform is only expressed in a very small subset of specialized muscles in adult large mammals, including humans.ResultsWe identify the DNA sequences limiting MyHC-IIb expression in humans and explore the activation of this gene in human skeletal muscle. We demonstrate that the transcriptional activity of ~1.0 kb of the human MyHC-IIb promoter is greatly reduced compared to that of the corresponding mouse sequence in both mouse and human myotubes in vitro and show that nucleotide differences that eliminate binding sites for myocyte enhancer factor 2 (MEF2) and serum response factor (SRF) account for this difference. Despite these differences, we show that MyHC-IIb mRNA is expressed in fetal human muscle cells and that MyHC-IIb mRNA is significantly up-regulated in the skeletal muscle of Duchene muscular dystrophy patients.ConclusionsThese data identify the genetic basis for a key phenotypic difference between the muscles of large and small mammals, and demonstrate that mRNA expression of the MyHC-IIb gene can be re-activated in human limb muscle undergoing profound degeneration/regeneration.

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