Suppressor of hairless directly activates transcription of enhancer of split complex genes in response to Notch receptor activity

Genes Dev. 1995 Nov 1;9(21):2609-22. doi: 10.1101/gad.9.21.2609.

Abstract

We have investigated the functional relationships among three loci that are required for multiple alternative cell fate decisions during adult peripheral neurogenesis in Drosophila: Notch (N), which encodes a transmembrane receptor protein, Suppressor of Hairless [Su(H)], which encodes a DNA-binding transcription factor, and the Enhancer of split gene complex [E(spl)-C], which includes seven transcription units that encode basic helix-loop-helix (bHLH) repressor proteins. We describe several lines of evidence establishing that Su(H) directly activates transcription of E(spl)-C genes in response to N receptor activity. Expression of an activated form of the N receptor leads to elevated and ectopic E(spl)-C transcript accumulation and promoter activity in imaginal discs. We show that the proximal upstream regions of three E(spl)-C genes contain multiple specific binding sites for Su(H). The integrity of these sites, as well as Su(H) gene activity, are required not only for normal levels of expression of E(spl)-C genes in imaginal disc proneural clusters, but also for their transcriptional response to hyperactivity of the N receptor. Our results establish Su(H) as a direct regulatory link between N receptor activity and the expression of E(spl)-C genes, extending the known linear structure of the N cell-cell signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • Basic Helix-Loop-Helix Transcription Factors
  • Binding Sites
  • Conserved Sequence
  • DNA-Binding Proteins / genetics*
  • Drosophila / genetics
  • Drosophila / growth & development
  • Drosophila Proteins*
  • Evolution, Molecular
  • Gene Expression Regulation, Developmental*
  • Helix-Loop-Helix Motifs / genetics
  • Insect Hormones / genetics*
  • Membrane Proteins / physiology*
  • Molecular Sequence Data
  • Nerve Tissue Proteins / genetics
  • Peripheral Nervous System / growth & development
  • Promoter Regions, Genetic
  • Receptors, Notch
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism
  • Signal Transduction
  • Transcription, Genetic*
  • Wings, Animal / growth & development

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • DNA-Binding Proteins
  • Drosophila Proteins
  • E(spl)mdelta-HLH protein, Drosophila
  • Insect Hormones
  • Membrane Proteins
  • N protein, Drosophila
  • Nerve Tissue Proteins
  • Receptors, Notch
  • Repressor Proteins
  • Su(H) protein, Drosophila