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.
Barolo
Scott
S
Division of Biological Sciences/Cell and Developmental Biology, University of California San Diego, La Jolla, California 92093-0349, USA.
Stone
Tammie
T
Bang
Anne G
AG
Posakony
James W
JW
D000429:Alcohol Oxidoreductases; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D001665:Binding Sites; D016384:Consensus Sequence; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D004331:Drosophila melanogaster / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D020868:Gene Silencing; D005799:Genes, Dominant; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000502:physiology; D010641:Phenotype; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D051880:Receptors, Notch; D011993:Recombinant Fusion Proteins / Q000502:physiology; D020449:Repetitive Sequences, Amino Acid; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors
D000429:Alcohol Oxidoreductases; D051792:Basic Helix-Loop-Helix Proteins; D004247:DNA; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D046911:Macromolecular Substances; D008565:Membrane Proteins; D010750:Phosphoproteins; D051880:Receptors, Notch; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C497759:N protein, Drosophila; C088731:Su(H) protein, Drosophila; C091023:gro protein, Drosophila; C076560:H protein, Drosophila; C096794:C-terminal binding protein