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

• Published in: Cell reports (Cambridge) 2016-08, Vol.16 (9), p.2308-2316
• Main Authors: Kang, Yuanyuan, Wang, Jianbin, Neff, Ashley, Kratzer, Stella, Kimura, Hiroshi, Davis, Richard E.
• Format: Article
• Language: English
• Subjects: Animals; Ascaris; Ascaris suum - genetics; Ascaris suum - growth & development; Ascaris suum - metabolism; Autoantigens - genetics; Autoantigens - metabolism; CENP-A; CENP-C; centromere; 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; holocentromere; kinetochore; Kinetochores - metabolism; Kinetochores - ultrastructure; Microtubules - metabolism; Microtubules - ultrastructure; Mitosis; NDC80; programmed DNA elimination
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2016.07.079

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. [Display omitted] •CENP-A genome distribution suggests that Ascaris has holocentric chromosomes•Genomic regions lost during somatic DNA elimination have reduced CENP-A level•CENP-A is present in these same genomic regions in the mitotic germline•Changes in CENP-A localization contribute to programmed DNA elimination Kang et al. show that nematodes with programmed DNA elimination have holocentric chromosomes in the mitotic germline. DNA sequences lost in early embryos during programmed DNA elimination have reduced levels of CENP-A and kinetochore components. Thus, developmental changes in CENP-A localization contribute to sequences lost in programmed DNA elimination.