The role of heterochromatin in centromere function

Philos Trans R Soc Lond B Biol Sci. 2005 Mar 29;360(1455):569-79. doi: 10.1098/rstb.2004.1611.

Abstract

Chromatin at centromeres is distinct from the chromatin in which the remainder of the genome is assembled. Two features consistently distinguish centromeres: the presence of the histone H3 variant CENP-A and, in most organisms, the presence of heterochromatin. In fission yeast, domains of silent "heterochromatin" flank the CENP-A chromatin domain that forms a platform upon which the kinetochore is assembled. Thus, fission yeast centromeres resemble their metazoan counterparts where the kinetochore is embedded in centromeric heterochromatin. The centromeric outer repeat chromatin is underacetylated on histones H3 and H4, and methylated on lysine 9 of histone H3, which provides a binding site for the chromodomain protein Swi6 (orthologue of Heterochromatin Protein 1, HP1). The remarkable demonstration that the assembly of repressive heterochromatin is dependent on the RNA interference machinery provokes many questions about the mechanisms of this process that may be tractable in fission yeast. Heterochromatin ensures that a high density of cohesin is recruited to centromeric regions, but it could have additional roles in centromere architecture and the prevention of merotely, and it might also act as a trigger for kinetochore assembly. In addition, we discuss an epigenetic model for ensuring that CENP-A is targeted and replenished at the kinetochore domain.

Publication types

  • Review

MeSH terms

  • Cell Cycle Proteins
  • Centromere / metabolism
  • Centromere / physiology*
  • Chromosomal Proteins, Non-Histone
  • Cohesins
  • Epigenesis, Genetic / physiology*
  • Fungal Proteins
  • Heterochromatin / metabolism
  • Heterochromatin / physiology*
  • Histones / metabolism
  • Kinetochores / metabolism*
  • Models, Biological*
  • Nuclear Proteins / metabolism
  • RNA Interference
  • Schizosaccharomyces

Substances

  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • Fungal Proteins
  • Heterochromatin
  • Histones
  • Nuclear Proteins