Histone H3 and H4 N-termini interact with SIR3 and SIR4 proteins: a molecular model for the formation of heterochromatin in yeast

Cell. 1995 Feb 24;80(4):583-92. doi: 10.1016/0092-8674(95)90512-x.


The silent mating loci and chromosomal regions adjacent to telomeres of S. cerevisiae have features similar to heterochromatin of more complex eukaryotes. Transcriptional repression at these sites depends on the silent information regulators SIR3 and SIR4 as well as histones H3 and H4. We show here that the SIR3 and SIR4 proteins interact with specific silencing domains of the H3 and H4 N-termini in vitro. Certain mutations in these factors, which affect their silencing functions in vivo, also disrupt their interactions in vitro. Immunofluorescence studies with antibodies against RAP1 and SIR3 demonstrate that the H3 and H4 N-termini are required for the association of SIR3 with telomeric chromatin and the perinuclear positioning of yeast telomeres. Based on these interactions, we propose a model for heterochromatin-mediated transcriptional silencing in yeast, which may serve as a paradigm for other eukaryotic organisms as well.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Cell Compartmentation
  • Cell Nucleus / ultrastructure
  • DNA Mutational Analysis
  • Fluorescent Antibody Technique
  • Fungal Proteins / metabolism*
  • Gene Expression Regulation, Fungal
  • Heterochromatin / metabolism*
  • Heterochromatin / ultrastructure
  • Histones / genetics
  • Histones / metabolism*
  • Mating Factor
  • Models, Molecular
  • Molecular Sequence Data
  • Peptide Biosynthesis
  • Peptides / genetics
  • Saccharomyces cerevisiae / genetics*
  • Silent Information Regulator Proteins, Saccharomyces cerevisiae*
  • Structure-Activity Relationship
  • Telomere / ultrastructure
  • Trans-Activators / metabolism*


  • Fungal Proteins
  • Heterochromatin
  • Histones
  • Peptides
  • SIR3 protein, S cerevisiae
  • SIR4 protein, S cerevisiae
  • Silent Information Regulator Proteins, Saccharomyces cerevisiae
  • Trans-Activators
  • Mating Factor