Sir2p and Sas2p opposingly regulate acetylation of yeast histone H4 lysine16 and spreading of heterochromatin

Nat Genet. 2002 Nov;32(3):378-83. doi: 10.1038/ng1017. Epub 2002 Oct 15.

Abstract

The Sir3 protein helps form telomeric heterochromatin by interacting with hypoacetylated histone H4 lysine 16 (H4-Lys16). The molecular nature of the heterochromatin boundary is still unknown. Here we show that the MYST-like acetyltransferase Sas2p is required for the acetylation (Ac) of H4-Lys16 in euchromatin. In a sas2Delta strain or a phenocopy Lys16Arg mutant, Sir3p spreads from roughly 3 kb to roughly 15 kb, causing hypoacetylation and repression of adjacent chromatin. We also found that disruption of Sir3p binding in a deacetylase-deficient Sir 2Delta strain can be suppressed by sas2Delta. These data indicate that opposing effects of Sir2p and Sas2p on acetylation of H4-Lys16 maintain the boundary at telomeric heterochromatin.

Publication types

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

MeSH terms

  • Acetylation
  • Acetyltransferases / metabolism
  • Acetyltransferases / physiology*
  • Arginine
  • Chromatin / metabolism
  • Heterochromatin / chemistry
  • Heterochromatin / metabolism*
  • Histone Acetyltransferases
  • Histone Deacetylases / metabolism
  • Histone Deacetylases / physiology*
  • Histones / metabolism*
  • Lysine / metabolism*
  • Mutation
  • Precipitin Tests
  • Promoter Regions, Genetic
  • Protein Binding
  • Protein Structure, Tertiary
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Saccharomyces cerevisiae Proteins / metabolism
  • Saccharomyces cerevisiae Proteins / physiology*
  • Silent Information Regulator Proteins, Saccharomyces cerevisiae / metabolism
  • Silent Information Regulator Proteins, Saccharomyces cerevisiae / physiology*
  • Sirtuin 2
  • Sirtuins / metabolism
  • Sirtuins / physiology*
  • Telomere / ultrastructure

Substances

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