MRF4 can substitute for myogenin during early stages of myogenesis

Dev Dyn. 1997 Jun;209(2):233-41. doi: 10.1002/(SICI)1097-0177(199706)209:2<233::AID-AJA9>3.0.CO;2-J.

Abstract

MRF4, myogenin, MyoD, and Myf-5 are the four members of the basic helix-loop-helix family of muscle-specific regulatory factors (MRFs). We examined whether MRF4 could substitute for myogenin in vivo by determining if the myofiber- and MRF4-deficient phenotype of myogenin (-/-) mice could be rescued by a myogenin promoter-MRF4 transgene. When the transgene was expressed at a physiological level in myogenin-deficient fetuses, we found that expression of the endogenous MRF4 gene was restored to normal levels, whereas MyoD levels were unchanged. Thus, MRF4 can participate in a positive autoregulatory loop and can substitute for myogenin to activate its own promoter. Myogenin-deficient fetuses that expressed the transgene also had more myosin, more and larger myofibers, and a more normal ribcage morphology than myogenin-deficient littermates without the transgene. The transgene failed, however, to restore normal numbers of myofibers or viability to myogenin-deficient mice, because the approximately 1.6 kb myogenin promoter fragment was not expressed in most late-forming myofibers. These results demonstrate that MRF4 is able to substitute for myogenin to activate MRF4 expression and promote myofiber formation during the early stages of myogenesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Gene Expression Regulation, Developmental
  • Mice
  • Mice, Transgenic
  • Muscle Fibers, Skeletal / physiology
  • Muscles / embryology*
  • MyoD Protein / metabolism
  • Myogenic Regulatory Factors / genetics
  • Myogenic Regulatory Factors / physiology*
  • Myogenin / physiology*
  • Phenotype
  • Promoter Regions, Genetic
  • Receptors, Cholinergic / metabolism
  • Transcription Factors / physiology*
  • Transgenes

Substances

  • MyoD Protein
  • Myog protein, mouse
  • Myogenic Regulatory Factors
  • Myogenin
  • Receptors, Cholinergic
  • Transcription Factors
  • myogenic factor 6