SIR2 is required for polycomb silencing and is associated with an E(Z) histone methyltransferase complex

Curr Biol. 2004 Oct 26;14(20):1812-21. doi: 10.1016/j.cub.2004.09.060.


Background: SIR2 was originally identified in S. cerevisiae for its role in epigenetic silencing through the creation of specialized chromatin domains. It is the most evolutionarily conserved protein deacetylase, with homologs in all kingdoms. SIR2 orthologs in multicellular eukaryotes have been implicated in lifespan determination and regulation of the activities of transcription factors and other proteins. Although SIR2 has not been widely implicated in epigenetic silencing outside yeast, Drosophila SIR2 mutations were recently shown to perturb position effect variegation, suggesting that the role of SIR2 in epigenetic silencing may not be restricted to yeast.

Results: Evidence is presented that Drosophila SIR2 is also involved in epigenetic silencing by the Polycomb group proteins. Sir2 mutations enhance the phenotypes of Polycomb group mutants and disrupt silencing of a mini-white reporter transgene mediated by a Polycomb response element. Consistent with this, SIR2 is physically associated with components of an E(Z) histone methyltransferase complex. SIR2 binds to many euchromatic sites on polytene chromosomes and colocalizes with E(Z) at most sites.

Conclusions: SIR2 is involved in the epigenetic inheritance of silent chromatin states mediated by the Drosophila Polycomb group proteins and is physically associated with a complex containing the E(Z) histone methyltransferase.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Blotting, Western
  • Crosses, Genetic
  • Drosophila
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila Proteins / physiology
  • Epigenesis, Genetic / physiology*
  • Fluorescent Antibody Technique
  • Gene Silencing / physiology*
  • Genes, Reporter / genetics
  • Histone Deacetylases / genetics
  • Histone Deacetylases / metabolism*
  • Histone Deacetylases / physiology
  • Histone Methyltransferases
  • Histone-Lysine N-Methyltransferase / metabolism
  • Immunoprecipitation
  • Molecular Sequence Data
  • Mutation / genetics
  • Nuclear Proteins / metabolism
  • Polycomb Repressive Complex 1
  • Polycomb Repressive Complex 2
  • Protein Methyltransferases
  • Repressor Proteins / metabolism
  • Sequence Alignment
  • Silent Information Regulator Proteins, Saccharomyces cerevisiae
  • Sirtuin 2
  • Sirtuins / genetics
  • Sirtuins / metabolism*
  • Sirtuins / physiology
  • Transgenes / genetics


  • Drosophila Proteins
  • Nuclear Proteins
  • Pc protein, Drosophila
  • Repressor Proteins
  • Silent Information Regulator Proteins, Saccharomyces cerevisiae
  • Histone Methyltransferases
  • Protein Methyltransferases
  • E(z) protein, Drosophila
  • Histone-Lysine N-Methyltransferase
  • Polycomb Repressive Complex 2
  • Polycomb Repressive Complex 1
  • SIR2 protein, S cerevisiae
  • Sirt2 protein, Drosophila
  • Sirtuin 2
  • Sirtuins
  • Histone Deacetylases