Local action of long-range repressors in the Drosophila embryo

EMBO J. 2001 May 1;20(9):2246-53. doi: 10.1093/emboj/20.9.2246.

Abstract

Previous studies have identified two corepressors in the early Drosophila embryo: Groucho and dCTBP: Both proteins are recruited to the DNA template by interacting with short peptide motifs conserved in a variety of sequence-specific transcriptional repressors. Once bound to DNA, Groucho appears to mediate long-range repression, while dCtBP directs short-range repression. The short-range Krüppel repressor was converted into a long-range repressor by replacing the dCtBP interaction motif (PxDLSxH) with a Groucho motif (WRPW). The resulting chimeric repressor causes a different mutant phenotype from that of the native Krüppel protein when misexpressed in transgenic embryos. The different patterning activities can be explained on the basis of long-range silencing within the hairy 5' regulatory region. The analysis of a variety of synthetic transgenes provides evidence that Groucho-dependent long-range repressors do not always cause the dominant silencing of linked enhancers within a complex cis-regulatory region. We suggest a "hot chromatin" model, whereby repressors require activators to bind DNA.

Publication types

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

MeSH terms

  • Alcohol Oxidoreductases
  • Amino Acid Motifs / physiology
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors
  • Body Patterning / genetics
  • DNA / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Drosophila
  • Drosophila Proteins*
  • Embryo, Nonmammalian / metabolism
  • Enhancer Elements, Genetic
  • Gene Silencing
  • Genes, Dominant
  • Insect Proteins / genetics
  • Kruppel-Like Transcription Factors
  • Models, Genetic
  • Phenotype
  • Phosphoproteins / metabolism*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Regulatory Sequences, Nucleic Acid
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Snail Family Transcription Factors
  • Transcription Factors / genetics
  • Transgenes

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • DNA-Binding Proteins
  • Drosophila Proteins
  • Insect Proteins
  • Kr protein, Drosophila
  • Kruppel-Like Transcription Factors
  • Phosphoproteins
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • Snail Family Transcription Factors
  • Transcription Factors
  • gro protein, Drosophila
  • hairy protein, Drosophila
  • sna protein, Drosophila
  • hairy protein, insect
  • DNA
  • Alcohol Oxidoreductases
  • C-terminal binding protein