期刊
GENES & DEVELOPMENT
卷 16, 期 15, 页码 1964-1976出版社
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.987402
关键词
Hairless; Suppressor of Hairless; Notch; Groucho; CtBP; corepressors; transcriptional repression; adaptor
资金
- NIGMS NIH HHS [GM62279, GM20123, F32 GM020123, R01 GM062279] Funding Source: Medline
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/coreprescor complex is essential for proper cell fate specification during Drosophila peripheral nervous system development.
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