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. Here, we demonstrate that h, a basic-helix-loop-helix (bHLH) protein, is a sequence-specific DNA-binding protein and transcriptional repressor. We identify the proneural gene achaete (ac) as a direct downstream target of h regulation in vivo. Mutation of a single, evolutionarily conserved, high-affinity h binding site in the upstream region of ac results in the appearance of ectopic sensory organs in adult flies, in a pattern that strongly resembles the phenotype of h mutants. This indicates that direct repression of ac by h plays an essential role in pattern formation in the PNS. Our results demonstrate that HLH proteins negatively regulate ac transcription by at least two distinct mechanisms.
Van Doren
M
M
Department of Biology, University of California San Diego, La Jolla 92093-0322.
Bailey
A M
AM
Esnayra
J
J
Ede
K
K
Posakony
J W
JW
D000818:Animals; D001483:Base Sequence; D004268:DNA-Binding Proteins; D004330:Drosophila / Q000235:genetics*; D005786:Gene Expression Regulation; D017344:Genes, Insect; D018257:Helix-Loop-Helix Motifs; D008969:Molecular Sequence Data; D009154:Mutation; D017933:Peripheral Nervous System / Q000196:embryology*; D012097:Repressor Proteins; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D012097:Repressor Proteins