Differential Chromosomal Localization of Centromeric Histone CENP-A Contributes to Nematode Programmed DNA Elimination

Cell Rep. 2016 Aug 30;16(9):2308-16. doi: 10.1016/j.celrep.2016.07.079. Epub 2016 Aug 18.

Abstract

The stability of the genome is paramount to organisms. However, diverse eukaryotes carry out programmed DNA elimination in which portions or entire chromsomes are lost in early development or during sex determination. During early development of the parasitic nematode, Ascaris suum, 13% of the genome is eliminated. How different genomic segments are reproducibly retained or discarded is unknown. Here, we show that centromeric histone CENP-A localization plays a key role in this process. We show that Ascaris chromosomes are holocentric during germline mitoses, with CENP-A distributed along their length. Prior to DNA elimination in the four-cell embryo, CENP-A is significantly diminished in chromosome regions that will be lost. This leads to the absence of kinetochores and microtubule attachment sites necessary for chromosome segregation, resulting in loss of these regions upon mitosis. Our data suggest that changes in CENP-A localization specify which portions of chromosomes will be lost during programmed DNA elimination.

Keywords: Ascaris; CENP-A; CENP-C; NDC80; centromere; chromosome segregation; holocentromere; kinetochore; programmed DNA elimination.

Publication types

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

MeSH terms

  • Animals
  • Ascaris suum / genetics*
  • Ascaris suum / growth & development
  • Ascaris suum / metabolism
  • Autoantigens / genetics*
  • Autoantigens / metabolism
  • Centromere / metabolism*
  • Centromere / ultrastructure
  • Centromere Protein A
  • Chromatin / metabolism
  • Chromatin / ultrastructure
  • Chromosomal Proteins, Non-Histone / genetics*
  • Chromosomal Proteins, Non-Histone / metabolism
  • Chromosome Mapping
  • Chromosome Segregation
  • Embryo, Nonmammalian
  • Gene Expression
  • Genome, Helminth*
  • Helminth Proteins / genetics*
  • Helminth Proteins / metabolism
  • Kinetochores / metabolism
  • Kinetochores / ultrastructure
  • Microtubules / metabolism
  • Microtubules / ultrastructure
  • Mitosis*

Substances

  • Autoantigens
  • Centromere Protein A
  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • Helminth Proteins