Transcription of the myogenic regulatory gene Mef2 in cardiac, somatic, and visceral muscle cell lineages is regulated by a Tinman-dependent core enhancer

The MADS-box transcription factor MEF2 is expressed specifically in develop ing cardiac, somatic, and visceral muscle cell lineages during Drosophila e mbryogenesis and is required for myoblast differentiation and muscle morpho genesis. To define the mechanisms that regulate Mef2 transcription, we have analyzed the Mef2 upstream region for sequences sufficient to recapitulate the expression pattern of the gene in Drosophila embryos. Here we describe a complex enhancer located 5.8 kb upstream of the Drosophila Mef2 gene tha t controls transcription in cardial cells of the dorsal vessel a subset of somatic muscle founder cells, and the visceral muscle cells. The core of th is enhancer contains two evolutionarily conserved binding sites for the hom eodomain protein Tinman (Tin), expressed in developing cardiac, somatic, an d visceral muscle lineages. Both Tin binding sites are required for enhance r activity in all three muscle cell lineages. Whereas the 285-bp enhancer c ore alone is sufficient for expression in cardiac cells, expression in soma tic founder cells and visceral muscle is dependent on the core enhancer plu s unique flanking sequences that include an evolutionarily conserved E box. These results reveal an essential role for Tin in activation of Mef2 trans cription in multiple myogenic lineages and demonstrate that transcriptional activity of Tin is dependent on combinatorial interactions with other fact ors unique to different muscle cell types. (C) 1999 Academic Press.