Negative regulation of proneural gene activity: hairy is a direct transcriptional repressor of achaete.

Abstract

hairy (A) 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 acbaete

The WRPW Motif of the Hairy-Related Basic Helix-Loop-Helix Repressor Proteins Acts as a 4-Amino-Acid Transcription Repression and Protein-Protein Interaction Domain

“…These fusion proteins were tested for transcriptional repressor activity by using a modified achaete promoter as the reporter (Fig. 1B), as the achaete promoter is a well-defined in vivo target for Hairy (8,56,75). Instead of the single binding site for Hairy-related proteins, the modified reporter has five Gal4 upstream activation sequences (UASs) substituted at the same position.…”

“…Because Hairy-related proteins repress transcription by binding to specific hexameric sites and not by competing with activator proteins for binding sites (2,56,71,75), they function as active repressors and therefore should have specific repression domains (15,37,56). We previously hypothesized that the WRPW (Trp-Arg-Pro-Trp) motif might function as a transcriptional repression domain because this motif is found at the carboxyl termini of all of the repressors and none of the activators (56).…”

“…The repressor bHLH proteins are Hairy-related proteins such as Hairy, the proteins of the Enhancer of Split [E(spl)] complex, and the homologous mammalian Hes proteins (2,19,23,32,41,43,56,61,62,70,71). These proteins antagonize the activator proteins and prevent differentiation by binding to specific class B or C sites and repressing transcription (2,32,54,56,70,73,75). Thus, Hairy-related proteins are distinct from the emc and Id HLH repressors, which lack basic regions and repress by forming non-DNA-binding heterodimers with the activator bHLH proteins (7,17,22,25,76,77).…”

atonal is a proneural gene for a subset of olfactory sense organs in Drosophila

“…The antagonistic factors encoded by the emc (Ellis et al 1990;Garrell & Modolell 1990) and hairy (Ohsako et al 1994;Van Doren et al 1994) genes have been shown to restrict the domain of AS-C gene expression and thereby ensure the development of sensory structures at stereotypically fixed locations on the body surface. emc is known to genetically interact with the AS-C genes (Moscoso del Prado & Garcia-Bellido 1984).…”

Opposing inputs by Hedgehog and Brinker define a stripe ofhairyexpression in theDrosophilaleg imaginal disc

“…On either side of each h domain, a stripe of ac expression demarcates the position of each leg microchaete bristle row (Orenic et al, 1993). h encodes a bHLH transcription factor (Rushlow et al, 1989) and is a direct repressor of ac expression (Ohsako et al, 1994;Van Doren et al, 1994). In the absence of h function, ac expression expands into the regions normally occupied by Hairy, broadening the microchaete proneural fields and resulting in disorganized bristle rows in the adult.…”