DNA deletion as a mechanism for developmentally programmed centromere loss

Nucleic Acids Res. 2016 Feb 29;44(4):1553-65. doi: 10.1093/nar/gkv1110. Epub 2015 Oct 25.

Abstract

A hallmark of active centromeres is the presence of the histone H3 variant CenH3 in the centromeric chromatin, which ensures faithful genome distribution at each cell division. A functional centromere can be inactivated, but the molecular mechanisms underlying the process of centromere inactivation remain largely unknown. Here, we describe the loss of CenH3 protein as part of a developmental program leading to the formation of the somatic nucleus in the eukaryote Paramecium. We identify two proteins whose depletion prevents developmental loss of CenH3: the domesticated transposase Pgm involved in the formation of DNA double strand cleavages and the Polycomb-like lysine methyltransferase Ezl1 necessary for trimethylation of histone H3 on lysine 9 and lysine 27. Taken together, our data support a model in which developmentally programmed centromere loss is caused by the elimination of DNA sequences associated with CenH3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoantigens / genetics*
  • Cell Division / genetics
  • Cell Nucleus / genetics
  • Centromere / genetics*
  • Centromere Protein A
  • Chromatin / genetics
  • Chromosomal Proteins, Non-Histone / genetics*
  • DNA / genetics*
  • DNA Breaks, Double-Stranded
  • Histones / genetics
  • Paramecium / genetics
  • Sequence Deletion / genetics*
  • Transposases / genetics

Substances

  • Autoantigens
  • Centromere Protein A
  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • Histones
  • DNA
  • Transposases