Chromosomes. CENP-C Reshapes and Stabilizes CENP-A Nucleosomes at the Centromere

Science. 2015 May 8;348(6235):699-703. doi: 10.1126/science.1259308.

Abstract

Inheritance of each chromosome depends upon its centromere. A histone H3 variant, centromere protein A (CENP-A), is essential for epigenetically marking centromere location. We find that CENP-A is quantitatively retained at the centromere upon which it is initially assembled. CENP-C binds to CENP-A nucleosomes and is a prime candidate to stabilize centromeric chromatin. Using purified components, we find that CENP-C reshapes the octameric histone core of CENP-A nucleosomes, rigidifies both surface and internal nucleosome structure, and modulates terminal DNA to match the loose wrap that is found on native CENP-A nucleosomes at functional human centromeres. Thus, CENP-C affects nucleosome shape and dynamics in a manner analogous to allosteric regulation of enzymes. CENP-C depletion leads to rapid removal of CENP-A from centromeres, indicating their collaboration in maintaining centromere identity.

Publication types

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

MeSH terms

  • Autoantigens / chemistry
  • Autoantigens / genetics
  • Autoantigens / metabolism*
  • Centromere / chemistry
  • Centromere / metabolism*
  • Centromere / ultrastructure
  • Centromere Protein A
  • Chromosomal Proteins, Non-Histone / chemistry
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism*
  • DNA / chemistry
  • DNA / metabolism
  • Epigenesis, Genetic
  • Fluorescence Resonance Energy Transfer
  • Gene Knockdown Techniques
  • Humans
  • Nucleosomes / chemistry
  • Nucleosomes / metabolism*
  • Nucleosomes / ultrastructure
  • Protein Structure, Secondary

Substances

  • Autoantigens
  • CENPA protein, human
  • Centromere Protein A
  • Chromosomal Proteins, Non-Histone
  • Nucleosomes
  • centromere protein C
  • DNA