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.

Abstract

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

Substances

  • 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