Ccp1 modulates epigenetic stability at centromeres and affects heterochromatin distribution in Schizosaccharomyces pombe

J Biol Chem. 2018 Aug 3;293(31):12068-12080. doi: 10.1074/jbc.RA118.003873. Epub 2018 Jun 13.


Distinct chromatin organization features, such as centromeres and heterochromatin domains, are inherited epigenetically. However, the mechanisms that modulate the accuracy of epigenetic inheritance, especially at the individual nucleosome level, are not well-understood. Here, using ChIP and next-generation sequencing (ChIP-Seq), we characterized Ccp1, a homolog of the histone chaperone Vps75 in budding yeast that functions in centromere chromatin duplication and heterochromatin maintenance in fission yeast (Schizosaccharomyces pombe). We show that Ccp1 is enriched at the central core regions of the centromeres. Of note, among all histone chaperones characterized, deletion of the ccp1 gene uniquely reduced the rate of epigenetic switching, manifested as position effect variegation within the centromeric core region (CEN-PEV). In contrast, gene deletion of other histone chaperones either elevated the PEV switching rates or did not affect centromeric PEV. Ccp1 and the kinetochore components Mis6 and Sim4 were mutually dependent for centromere or kinetochore association at the proper levels. Moreover, Ccp1 influenced heterochromatin distribution at multiple loci in the genome, including the subtelomeric and the pericentromeric regions. We also found that Gar2, a protein predominantly enriched in the nucleolus, functions similarly to Ccp1 in modulating the epigenetic stability of centromeric regions, although its mechanism remained unclear. Together, our results identify Ccp1 as an important player in modulating epigenetic stability and maintaining proper organization of multiple chromatin domains throughout the fission yeast genome.

Keywords: centromere; epigenetic stability; epigenetics; fission yeast; heterochromatin; histone chaperone; yeast.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Centromere / metabolism*
  • Centromere / ultrastructure
  • Chromatin Assembly and Disassembly
  • Chromosome Segregation
  • Chromosomes, Fungal / metabolism*
  • Chromosomes, Fungal / ultrastructure
  • Epigenesis, Genetic*
  • Genomic Instability
  • Heterochromatin / metabolism*
  • Heterochromatin / ultrastructure
  • Molecular Chaperones / genetics*
  • Molecular Chaperones / metabolism
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Nucleosomes / metabolism
  • Nucleosomes / ultrastructure
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Schizosaccharomyces / genetics*
  • Schizosaccharomyces / metabolism
  • Schizosaccharomyces pombe Proteins / genetics
  • Schizosaccharomyces pombe Proteins / metabolism


  • Cell Cycle Proteins
  • GAR2 protein, S pombe
  • Heterochromatin
  • Mis6 protein, S pombe
  • Molecular Chaperones
  • Nuclear Proteins
  • Nucleosomes
  • Repressor Proteins
  • Saccharomyces cerevisiae Proteins
  • Schizosaccharomyces pombe Proteins
  • Vps75 protein, S cerevisiae