RESUMO
Changes in gene regulatory networks are a major engine for creating developmental novelty during evolution. Conversely, regulatory linkages that survive for very long evolutionary periods might be characteristic of ancient and abstract functions of fundamental utility to all metazoans. The proneural genes, which encode a distinctive family of basic helix-loop-helix (bHLH) transcriptional activators, act to promote neural cell fates in the ectoderm of diverse species. Here we report that these genes have been associated for at least 600-700 million years--since before the cnidarian/bilaterian divergence--with a high-affinity binding site for Hairy/Enhancer of split (Hes) repressor proteins. We suggest that the systematic identification of such ancient and conserved connections will be a powerful means of uncovering the primordial functions of transcription factors and signaling systems.
Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Evolução Molecular , Filogenia , Proteínas Repressoras/genética , Transcrição Gênica , Animais , Sequência de Bases , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Sítios de Ligação , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Insetos/genética , Dados de Sequência Molecular , Ratos , Proteínas Repressoras/metabolismoRESUMO
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.