Default repression and Notch signaling: Hairless acts as an adaptor to recruit the corepressors Groucho and dCtBP to Suppressor of Hairless.

The DNA-binding transcription factor Suppressor of Hairless [Su(H)] functions as an activator during Notch (N) pathway signaling, but can act as a repressor in the absence of signaling. Hairless (H), a novel Drosophila protein, binds to Su(H) and has been proposed to antagonize N signaling by inhibiting DNA binding by ...
Su(H). Here we show that, in vitro, H directly binds two corepressor proteins, Groucho (Gro) and dCtBP. Reduction of gro or dCtBP function enhances H mutant phenotypes and suppresses N phenotypes in the adult mechanosensory bristle. This activity of gro is surprising, because it is directed oppositely to its traditionally defined role as a neurogenic gene. We find that Su(H)-H complexes can bind to DNA with high efficiency in vitro. Furthermore, a H-VP16 fusion protein causes dominant-negative phenotypes in vivo, a result consistent with the proposal that H functions in transcriptional repression. Taken together, our findings indicate that "default repression" of N pathway target genes by an unusual adaptor/corepressor complex is essential for proper cell fate specification during Drosophila peripheral nervous system development.
Mesh Terms:
Alcohol Oxidoreductases, Amino Acid Motifs, Amino Acid Sequence, Animals, Basic Helix-Loop-Helix Transcription Factors, Binding Sites, Consensus Sequence, DNA, DNA-Binding Proteins, Drosophila Proteins, Drosophila melanogaster, Gene Expression Regulation, Gene Silencing, Genes, Dominant, Macromolecular Substances, Membrane Proteins, Phenotype, Phosphoproteins, Protein Binding, Protein Interaction Mapping, Protein Structure, Tertiary, Receptors, Notch, Recombinant Fusion Proteins, Repetitive Sequences, Amino Acid, Repressor Proteins, Signal Transduction, Transcription Factors
Genes Dev.
Date: Aug. 01, 2002
Download Curated Data For This Publication
Switch View:
  • Interactions 11