The helix‐loop‐helix domain: A common motif for bristles, muscles and sex

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Abstract
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.