Epigenetic, genetic and maternal effects enable stable centromere inheritance

Nat Cell Biol. 2022 May;24(5):748-756. doi: 10.1038/s41556-022-00897-w. Epub 2022 May 9.


Centromeres are defined epigenetically by the histone H3 variant CENP-A. The propagation cycle by which pre-existing CENP-A nucleosomes serve as templates for nascent assembly predicts the epigenetic memory of weakened centromeres. Using a mouse model with reduced levels of CENP-A nucleosomes, we find that an embryonic plastic phase precedes epigenetic memory through development. During this phase, nascent CENP-A nucleosome assembly depends on the maternal Cenpa genotype rather than the pre-existing template. Weakened centromeres are thus limited to a single generation, and parental epigenetic differences are eliminated by equal assembly on maternal and paternal centromeres. These differences persist, however, when the underlying DNA of parental centromeres differs in repeat abundance, as assembly during the plastic phase also depends on sufficient repetitive centromere DNA. With contributions of centromere DNA and the Cenpa maternal effect, we propose that centromere inheritance naturally minimizes fitness costs associated with weakened centromeres or epigenetic differences between parents.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Autoantigens / genetics
  • Cell Cycle Proteins / genetics
  • Centromere / genetics
  • Centromere / metabolism
  • Centromere Protein A / genetics
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism
  • Epigenesis, Genetic
  • Histones / genetics
  • Histones / metabolism
  • Maternal Inheritance* / genetics
  • Nucleosomes* / genetics
  • Plastics


  • Autoantigens
  • Cell Cycle Proteins
  • Centromere Protein A
  • Chromosomal Proteins, Non-Histone
  • Histones
  • Nucleosomes
  • Plastics