The helix-loop-helix domain: a common motif for bristles, muscles and sex

Three apparently unrelated developmental processes--mammalian myogenesis, the choice of neural fate and sex determination in Drosophila--are controlled by a common mechanism. Most of the genes governing these processes encode transcriptional factors that contain the helix-loop-helix (HLH) motif. This domain mediates the formation of homo- or heterodimers that specifically bind to DNA through a conserved basic region adjacent to the HLH motif. Dimers differ in their affinity for DNA and in their ability to activate transcription from HLH binding-site containing promoters. In addition, the activity of HLH proteins is inhibited by dimerization with another class of HLH proteins that lack a basic domain entirely or have an altered one. These structural properties provide a molecular mechanism to explain the synergistic and antagonistic functional relations among the HLH encoding genes that control several developmental pathways.