title: Differential Chromosomal Localization of Centromeric Histone CENP-A Contributes to Nematode Programmed DNA Elimination.
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.
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, CO 80045, USA.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Kang
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, CO 80045, USA.
authors.forename: Jianbin
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, CO 80045, USA.
authors.forename: Ashley
authors.initials: A
authors.lastname: Neff
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, CO 80045, USA.
authors.forename: Stella
authors.initials: S
authors.lastname: Kratzer
authors.affiliation: Department of Biological Sciences, Tokyo Institute of Technology, Tokyo 152-8550, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kimura
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, CO 80045, USA. Electronic address: richard.davis@ucdenver.edu.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Davis
mesh_terms: D000818:Animals; D017165:Ascaris suum / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D001324:Autoantigens / Q000235:genetics* / Q000378:metabolism; D002503:Centromere / Q000378:metabolism* / Q000648:ultrastructure; D000076247:Centromere Protein A; D002843:Chromatin / Q000378:metabolism / Q000648:ultrastructure; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics* / Q000378:metabolism; D002874:Chromosome Mapping; D020090:Chromosome Segregation; D004625:Embryo, Nonmammalian; D015870:Gene Expression; D049751:Genome, Helminth; D015801:Helminth Proteins / Q000235:genetics* / Q000378:metabolism; D018386:Kinetochores / Q000378:metabolism / Q000648:ultrastructure; D008870:Microtubules / Q000378:metabolism / Q000648:ultrastructure; D008938:Mitosis
chemical_list: D001324:Autoantigens; D000076247:Centromere Protein A; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D015801:Helminth Proteins
keywords: Ascaris; CENP-A; CENP-C; NDC80; centromere; chromosome segregation; holocentromere; kinetochore; programmed DNA elimination