Clustering heterochromatin: Sir3 promotes telomere clustering independently of silencing in yeast

J Cell Biol. 2011 Feb 7;192(3):417-31. doi: 10.1083/jcb.201008007.

Abstract

A general feature of the nucleus is the organization of repetitive deoxyribonucleic acid sequences in clusters concentrating silencing factors. In budding yeast, we investigated how telomeres cluster in perinuclear foci associated with the silencing complex Sir2-Sir3-Sir4 and found that Sir3 is limiting for telomere clustering. Sir3 overexpression triggers the grouping of telomeric foci into larger foci that relocalize to the nuclear interior and correlate with more stable silencing in subtelomeric regions. Furthermore, we show that Sir3's ability to mediate telomere clustering can be separated from its role in silencing. Indeed, nonacetylable Sir3, which is unable to spread into subtelomeric regions, can mediate telomere clustering independently of Sir2-Sir4 as long as it is targeted to telomeres by the Rap1 protein. Thus, arrays of Sir3 binding sites at telomeres appeared as the sole requirement to promote trans-interactions between telomeres. We propose that similar mechanisms involving proteins able to oligomerize account for long-range interactions that impact genomic functions in many organisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Gene Expression Regulation, Fungal
  • Gene Silencing*
  • Heterochromatin / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Shelterin Complex
  • Silent Information Regulator Proteins, Saccharomyces cerevisiae / genetics*
  • Silent Information Regulator Proteins, Saccharomyces cerevisiae / metabolism
  • Sirtuin 2 / genetics
  • Sirtuin 2 / metabolism
  • Telomere / genetics
  • Telomere / metabolism*
  • Telomere-Binding Proteins / genetics
  • Telomere-Binding Proteins / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Heterochromatin
  • RAP1 protein, S cerevisiae
  • SIR3 protein, S cerevisiae
  • SIR4 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Shelterin Complex
  • Silent Information Regulator Proteins, Saccharomyces cerevisiae
  • Telomere-Binding Proteins
  • Transcription Factors
  • SIR2 protein, S cerevisiae
  • Sirtuin 2