THE MYOGENIC REGULATORY GENE MEF2 IS A DIRECT TARGET FOR TRANSCRIPTIONAL ACTIVATION BY TWIST DURING DROSOPHILA MYOGENESIS

MEF2 is a MADS-box transcription factor required for muscle developmen t in Drosophila. Here, we show that the bHLH transcription factor Twis t directly regulates Mef2 expression in adult somatic muscle precursor cells via a 175-bp enhancer located 2245 bp upstream of the transcrip tional start site. Within this element, a single evolutionarily conser ved E box is essential for enhancer activity. Twist protein can bind t o this E box to activate Mef2 transcription, and ectopic expression of twist results in ectopic activation of the wild-type 175-bp enhancer. By use of a temperature-sensitive mutant of twist, we show that activ ation of Mef2 transcription via this enhancer by Twist is required for normal adult muscle development, and reduction in Twist function resu lts in phenotypes similar to those observed previously in Mef2 mutant adults. The 175-bp enhancer is also active in the embryonic mesoderm, indicating that this enhancer functions at multiple times during devel opment, and its function is dependent on the same conserved E box. In embryos, a reduction in Twist function also strongly reduced Mef2 expr ession. These findings define a novel transcriptional pathway required for skeletal muscle development and identify Twist as an essential an d direct regulator of Mef2 expression in the somatic mesoderm.