Drosophila Sir2 is required for heterochromatic silencing and by euchromatic Hairy/E(Spl) bHLH repressors in segmentation and sex determination

Cell. 2002 May 17;109(4):447-58. doi: 10.1016/s0092-8674(02)00732-8.

Abstract

Yeast SIR2 is a NAD+-dependent histone deacetylase required for heterochromatic silencing at telomeres, rDNA, and mating-type loci. We find that the Drosophila homolog of Sir2 (dSir2) also encodes deacetylase activity and is required for heterochromatic silencing, but unlike ySir2, is not required for silencing at telomeres. We show that dSir2 interacts genetically and physically with members of the Hairy/Deadpan/E(Spl) family of bHLH euchromatic repressors, key regulators of Drosophila development. dSir2 is an essential gene whose loss of function results in both segmentation defects and skewed sex ratios, associated with reduced activities of the Hairy and Deadpan bHLH repressors. These results indicate that Sir2 in higher organisms plays an essential role in both euchromatic repression and heterochromatic silencing.

Publication types

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

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors
  • Body Patterning / genetics*
  • Drosophila Proteins*
  • Drosophila melanogaster / embryology*
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / metabolism
  • Embryo, Nonmammalian / abnormalities*
  • Embryo, Nonmammalian / cytology
  • Embryo, Nonmammalian / metabolism
  • Euchromatin / genetics
  • Female
  • Gene Expression Regulation, Developmental / genetics
  • Gene Expression Regulation, Enzymologic / genetics
  • Gene Silencing / physiology*
  • Helix-Loop-Helix Motifs / genetics
  • Heterochromatin / genetics
  • Histone Deacetylases / genetics*
  • Histone Deacetylases / metabolism
  • Insect Proteins / genetics*
  • Insect Proteins / metabolism
  • Male
  • Mutation / genetics
  • NAD / genetics
  • NAD / metabolism
  • Protein Binding / genetics
  • Protein Structure, Tertiary / genetics
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism
  • Sex Determination Processes*
  • Sex Factors
  • Silent Information Regulator Proteins, Saccharomyces cerevisiae*
  • Sirtuin 2
  • Sirtuins
  • Trans-Activators / genetics*
  • Trans-Activators / metabolism

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Drosophila Proteins
  • Euchromatin
  • Heterochromatin
  • Insect Proteins
  • Repressor Proteins
  • Silent Information Regulator Proteins, Saccharomyces cerevisiae
  • Trans-Activators
  • hairy protein, Drosophila
  • NAD
  • hairy protein, insect
  • SIR2 protein, S cerevisiae
  • Sirt2 protein, Drosophila
  • Sirtuin 2
  • Sirtuins
  • Histone Deacetylases