Long- and short-range transcriptional repressors induce distinct chromatin states on repressed genes

Curr Biol. 2011 Mar 8;21(5):406-12. doi: 10.1016/j.cub.2011.01.054. Epub 2011 Feb 25.


Transcriptional repression is essential for establishing precise patterns of gene expression during development. Repressors governing early Drosophila segmentation can be classified as short- or long-range factors based on their ranges of action, acting either locally to quench adjacent activators or broadly to silence an entire locus. Paradoxically, these repressors recruit common corepressors, Groucho and CtBP, despite their different ranges of repression. To reveal the mechanisms underlying these two distinct modes of repression, we performed chromatin analysis using the prototypical long-range repressor Hairy and the short-range repressor Knirps. Chromatin immunoprecipitation and micrococcal nuclease mapping studies reveal that Knirps causes local changes of histone density and acetylation, and the inhibition of activator recruitment, without affecting the recruitment of basal transcriptional machinery. In contrast, Hairy induces widespread histone deacetylation and inhibits the recruitment of basal machinery without inducing chromatin compaction. Our study provides detailed mechanistic insight into short- and long-range repression on selected endogenous target genes and suggests that the transcriptional corepressors can be differentially deployed to mediate chromatin changes in a context-dependent manner.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acetylation
  • Alcohol Oxidoreductases / metabolism
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Chromatin / physiology*
  • Chromatin Immunoprecipitation
  • DNA-Binding Proteins / metabolism
  • Drosophila / embryology*
  • Drosophila Proteins / metabolism*
  • Gene Expression Regulation, Developmental / genetics*
  • Gene Expression Regulation, Developmental / physiology
  • Histones / metabolism*
  • In Situ Hybridization
  • Micrococcal Nuclease / metabolism
  • Plasmids / genetics
  • Polymerase Chain Reaction
  • Repressor Proteins / metabolism*
  • Silencer Elements, Transcriptional / genetics*
  • Silencer Elements, Transcriptional / physiology


  • Basic Helix-Loop-Helix Transcription Factors
  • Chromatin
  • DNA-Binding Proteins
  • Drosophila Proteins
  • Histones
  • Repressor Proteins
  • gro protein, Drosophila
  • hairy protein, Drosophila
  • kni protein, Drosophila
  • Alcohol Oxidoreductases
  • C-terminal binding protein
  • Micrococcal Nuclease