The neurogenic suppressor of hairless DNA-binding protein mediates the transcriptional activation of the enhancer of split complex genes triggered by Notch signaling.
The Notch protein (N) acts as a transmembrane receptor for intercellular signals controlling cell fate choices in vertebrates and invertebrates. The signal of N activation may be transduced directly from the cell surface into the nucleus by an evolutionarily conserved transcription factor, Suppressor of Hairless [Su(H)], by its regulated nuclear import. Su(H) is shown here to play a direct role in the immediate response of the genome to N signaling in Drosophila. First, Su(H) mutant embryos derived from mutant germ-line clones exhibited a "neurogenic" phenotype of neural hypertrophy similar to the N phenotype. Second, the lack of N lateral signaling in these Su(H) mutant embryos was associated with a failure to express the m5 and m8 genes from the Enhancer of split Complex [E(spl)-C]. Finally, the Su(H) protein bound to the regulatory sequences of the E(spl)-C m5 and m8 genes, and these binding sites were required for the activation of the m5 and m8 promoters in the ventral neuroectoderm. The expression of the E(spl)-C m8 gene was found to be similarly regulated by Su(H) during wing imaginal disc development. Thus, the transcriptional activation of these E(spl)-C genes by Su(H) appears to be a direct and relatively general response to the activation of N. However, we also present evidence indicating that N signals in an Su(H)-independent manner during mesectoderm formation.
Lecourtois
M
M
Institut Jacques Monod, Centre National de la Recherche Scientifique (CNRS), Université Paris 7, France.
Schweisguth
F
F
D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000235:genetics; D004330:Drosophila / Q000235:genetics; D029721:Drosophila Proteins; D004475:Ectoderm / Q000502:physiology; D004625:Embryo, Nonmammalian / Q000502:physiology; D004627:Embryonic Induction / Q000235:genetics; D004742:Enhancer Elements, Genetic; D018507:Gene Expression Regulation, Developmental; D016153:Genes, Suppressor; D018257:Helix-Loop-Helix Motifs / Q000235:genetics; D006720:Homozygote; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D009154:Mutation; D009420:Nervous System / Q000196:embryology*; D009687:Nuclear Proteins / Q000235:genetics; D051880:Receptors, Notch; D012045:Regulatory Sequences, Nucleic Acid; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic; D001616:beta-Galactosidase / Q000235:genetics
D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D008565:Membrane Proteins; D009687:Nuclear Proteins; D051880:Receptors, Notch; D012097:Repressor Proteins; D001616:beta-Galactosidase; C497759:N protein, Drosophila; C088731:Su(H) protein, Drosophila; C089449:sim protein, Drosophila