Myocyte enhancer factor 2 and chorion factor 2 collaborate in activation of the myogenic program in Drosophila

The process of myogenesis requires the coordinated activation of many structural genes whose products are required for myofibril assembly, function, and regulation. Although numerous reports have documented the importance of the myogenic regulator myocyte enhancer factor 2 (MEF2) in muscle differentiation, the interaction of MEF2 with cofactors is critical to the realization of muscle fate. We identify here a genomic region required for full MEF2-mediated activation of actin gene expression in Drosophila, and we identify the zinc finger transcriptional regulator chorion factor 2 (CF2) as a factor functioning alongside MEF2 via this region. Furthermore, although both MEF2 and CF2 can individually activate actin gene expression, we demonstrate that these two factors collaborate in regulating the Actin57B target gene in vitro and in vivo. More globally, MEF2 and CF2 synergistically activate the enhancers of a number of muscle-specific genes, and loss of CF2 function in vivo results in reductions in the levels of several muscle structural gene transcripts. These findings validate a general importance of CF2 alongside MEF2 as a critical regulator of the myogenic program, identify a new regulator functioning with MEF2 to control cell fate, and provide insight into the network of regulatory events that shape the developing musculature.