Domains Outside of the DNA-Binding Domain Impart Target Gene Specificity to Myogenin and MRF4

Myogenin and MRF4 belong to the MyoD family of muscle-specific transcription factors, which can activate myogenesis when introduced into nonmyogenic cells. These proteins share homology within a basic-helix-loop-helix motif that mediates DNA binding and dimerization, but they are divergent in their amino and carboxyl termini. Although myogenin and MRF4 bind the same sequence within the muscle creatine kinase enhancer, only myogenin efficiently transactivates this enhancer. By creating chimeras of myogenin and MRF4, we show that the specificities of these factors for transactivation of the muscle creatine kinase enhancer can be interchanged by swapping their amino and carboxyl termini. Within these chimeras, strong cooperation between the amino and carboxyl termini was observed. These findings suggest that myogenin and MRF4 discriminate between muscle-specific enhancers and that target gene specificity is determined by domains surrounding the basic-helix-loop-helix region.