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Publication : MRF4 can substitute for myogenin during early stages of myogenesis.

First Author  Zhu Z Year  1997
Journal  Dev Dyn Volume  209
Issue  2 Pages  233-41
PubMed ID  9186058 Mgi Jnum  J:40798
Mgi Id  MGI:892176 Doi  10.1002/(SICI)1097-0177(199706)209:2<233::AID-AJA9>3.0.CO;2-J
Citation  Zhu Z, et al. (1997) MRF4 can substitute for myogenin during early stages of myogenesis. Dev Dyn 209(2):233-41
abstractText  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.
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