Default repression and Notch signaling: Hairless acts as an adaptor to recruit the corepressors Groucho and dCtBP to Suppressor of Hairless
Abstract
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 Nphenotypes in the adult mechanosensory bristle. This activity ofgro 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.
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Footnotes
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↵1 Present address: Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA
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↵2 Corresponding author.
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EMAIL: jposakony{at}ucsd.edu; FAX (858) 534-0566.
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Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.987402.
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- Received February 25, 2002.
- Accepted June 3, 2002.
- Cold Spring Harbor Laboratory Press