Constitutive centromere-associated network contacts confer differential stability on CENP-A nucleosomes in vitro and in the cell

Mol Biol Cell. 2018 Mar 15;29(6):751-762. doi: 10.1091/mbc.E17-10-0596. Epub 2018 Jan 17.


Eukaryotic centromeres are defined by the presence of nucleosomes containing the histone H3 variant, centromere protein A (CENP-A). Once incorporated at centromeres, CENP-A nucleosomes are remarkably stable, exhibiting no detectable loss or exchange over many cell cycles. It is currently unclear whether this stability is an intrinsic property of CENP-A containing chromatin or whether it arises from proteins that specifically associate with CENP-A chromatin. Two proteins, CENP-C and CENP-N, are known to bind CENP-A human nucleosomes directly. Here we test the hypothesis that CENP-C or CENP-N stabilize CENP-A nucleosomes in vitro and in living cells. We show that CENP-N stabilizes CENP-A nucleosomes alone and additively with CENP-C in vitro. However, removal of CENP-C and CENP-N from cells, or mutating CENP-A so that it no longer interacts with CENP-C or CENP-N, had no effect on centromeric CENP-A stability in vivo. Thus, the stability of CENP-A nucleosomes in chromatin does not arise solely from its interactions with CENP-C or CENP-N.

Publication types

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

MeSH terms

  • Cell Cycle
  • Cell Line
  • Centromere Protein A / genetics
  • Centromere Protein A / metabolism*
  • Chromatin / metabolism
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Histones / metabolism
  • Humans
  • Nucleosomes / genetics
  • Nucleosomes / metabolism*


  • CENPA protein, human
  • CENPN protein, human
  • Centromere Protein A
  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • Histones
  • Nucleosomes
  • centromere protein C