Distal regulatory elements control MRF4 gene expression in early and late myogenic cell populations.

MRF4 is a muscle-specific transcription factor that belongs to a family of basic helix-loop-helix proteins known as the myogenic regulatory factors (MRFs). In vitro studies have shown that expression of the MRF4 gene is controlled by a proximal promoter element (-336 to +71) that binds the muscle-specific transcription factors MEF2 and myogenin to activate transcription. To examine further the regulatory elements necessary for endogenous MRF4 gene expression during development, transgenic mice were generated that contained either a proximal MRF4 promoter-LacZ reporter gene (-336 MRF4-nLacZ) or a MRF4-LacZ reporter gene containing 8.

Transcription factor families: muscling in on the myogenic program.

Embryonic skeletal muscle development has become a paradigm for understanding the molecular basis of how cell lineages are established and how cells differentiate into specialized structures. Most vertebrate muscles are derived from individual somites that produce two distinct muscle populations: the myotomal muscles that generate the axial and trunk musculature and a second migratory cell population that colonizes regions of the developing limbs. In both instances, muscle differentiation is accompanied by cell cycle arrest, fusion of individual myoblasts into multinucleate myotubes, and the transcriptional activation of muscle-specific genes.

Myogenin and MEF2 function synergistically to activate the MRF4 promoter during myogenesis.

The basic helix-loop-helix muscle regulatory factor (MRF) gene family encodes four distinct muscle-specific transcription factors known as MyoD, myogenin, Myf-5, and MRF4. These proteins represent key regulatory factors that control many aspects of skeletal myogenesis. Although the MRFs often exhibit overlapping functional activities, their distinct expression patterns during embryogenesis suggest that each protein plays a unique role in controlling aspects of muscle development.

Cloning and expression of the axolotl proto-oncogene ski.

In vitro and in vivo overexpression studies have demonstrated that the c-ski proto-oncogene can influence proliferation, morphological transformation and myogenic differentiation. We report the isolation and expression of an axolotl (Ambystoma mexicanum) c-ski (aski) gene. Sequence analysis revealed a high degree of nucleotide and predicted amino acid (AA) homology with mammalian and anuran c-ski, showing the highest conservation to Xenopus laevis c-ski (74% nucleotide and 87% AA).

Overexpression of XMyoD or XMyf5 in Xenopus embryos induces the formation of enlarged myotomes through recruitment of cells of nonsomitic lineage.

The myogenic regulatory factors (MRFs) MyoD and Myf5 are the earliest described muscle-specific genes to be expressed in Xenopus development. To study the in vivo effects of overexpressing Xenopus MyoD and Myf5, synthetic RNAs were microinjected into single blastomeres of 2- to 32-cell stage Xenopus embryos. In vivo overexpression of these MRFs initiates the precocious and ectopic expression of actin and myosin.