Chromosomal gradient of histone acetylation established by Sas2p and Sir2p functions as a shield against gene silencing

Nat Genet. 2002 Nov;32(3):370-7. doi: 10.1038/ng993. Epub 2002 Oct 15.


Genes located in chromosomal regions near telomeres are transcriptionally silent, whereas those located in regions away from telomeres are not. Here we show that there is a gradient of acetylation of histone H4 at lysine 16 (H4-Lys16) along a yeast chromosome; this gradient ranges from a hypoacetylated state in regions near the telomere to a hyperacetylated state in more distant regions. The hyperacetylation is regulated by Sas2p, a member of the MYST-type family of histone acetylases, whereas hypoacetylation is under the control of Sir2p, a histone deacetylase. Loss of hyperacetylation is accompanied by an increase in localization of the telomere protein Sir3p and the inactivation of gene expression in telomere-distal regions. Thus, the Sas2p and Sir2p function in concert to regulate transcription in yeast, by acetylating and deacetylating H4-Lys16 in a mechanism that may be common to all eukaryotes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Acetyltransferases / genetics
  • Acetyltransferases / metabolism*
  • Acetyltransferases / physiology*
  • Blotting, Western
  • Chromatin / metabolism
  • Chromosomes / metabolism*
  • Chromosomes / ultrastructure
  • Gene Deletion
  • Gene Expression Regulation
  • Gene Silencing*
  • Genes, Fungal
  • Histone Acetyltransferases
  • Histone Deacetylases / genetics
  • Histone Deacetylases / physiology*
  • Histones / genetics
  • Histones / metabolism*
  • Lysine / chemistry
  • Models, Biological
  • Mutation
  • Oligonucleotide Array Sequence Analysis
  • Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Saccharomyces cerevisiae Proteins / physiology*
  • Silent Information Regulator Proteins, Saccharomyces cerevisiae / genetics
  • Silent Information Regulator Proteins, Saccharomyces cerevisiae / physiology*
  • Sirtuin 2
  • Sirtuins / genetics
  • Sirtuins / physiology*
  • Telomere / ultrastructure
  • Temperature


  • Chromatin
  • Histones
  • SIR3 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Silent Information Regulator Proteins, Saccharomyces cerevisiae
  • Acetyltransferases
  • Histone Acetyltransferases
  • Sas2 protein, S cerevisiae
  • SIR2 protein, S cerevisiae
  • Sirtuin 2
  • Sirtuins
  • Histone Deacetylases
  • Lysine