NEGATIVE REGULATION OF PRONEURAL GENE ACTIVITY - HAIRY IS A DIRECT TRANSCRIPTIONAL REPRESSOR OF ACHAETE

hairy (h) acts as a negative regulator in both embryonic segmentation and adult peripheral nervous system (PNS) development in Drosophila. H ere, we demonstrate that h, a basic-helix-loop-helix (bHLH) protein, i s a sequence-specific DNA-binding protein and transcriptional represso r. We identify the proneural gene achaete (ac) as a direct downstream target of h regulation in vivo. Mutation of a single, evolutionarily c onserved, high-affinity h binding site in the upstream region of ac re sults in the appearance of ectopic sensory organs in adult flies, in a pattern that strongly resembles the phenotype of h mutants. This indi cates that direct repression of ac by h plays an essential role in pat tern formation in the PNS. Our results demonstrate that HLH proteins n egatively regulate ac transcription by at least two distinct mechanism s.