When the mammalian skeletal-muscle-specific transcription factors MyoD, myogenin,
myf5 and MRF4, were first identified and shown to have the potential to activate myogenesis in nonmyogenic cell types, the molecular basis for establishment of the muscle phenotype seemed satisfyingly simple. These proteins share a 70-amino-acid region of homology that encompass a basic-helix-loop-helix (BHLH) motif that mediates oligomerization and binding to a conserved DNA sequence. That this conserved sequence is associated with most muscle-specific genes, seemed sufficient to explain the mechanism for activation of the set of genetically unlinked genes that is induced during myogenesis...