title: HACking the centromere chromatin code: insights from human artificial chromosomes.
abstract: The centromere is a specialized chromosomal region that serves as the assembly site of the kinetochore. At the centromere, CENP-A nucleosomes form part of a chromatin landscape termed centrochromatin. This chromatin environment conveys epigenetic marks regulating kinetochore formation. Recent work sheds light on the intricate relationship between centrochromatin state, the CENP-A assembly pathway and the maintenance of centromere function. Here, we review the emerging picture of how chromatin affects mammalian kinetochore formation. We place particular emphasis on data obtained from Human Artificial Chromosome (HAC) biology and the targeted engineering of centrochromatin using synthetic HACs. We discuss implications of these findings, which indicate that a delicate balance of histone modifications and chromatin state dictates both de novo centromere formation and the maintenance of centromere identity in dividing cell populations.
authors: Cold Spring Harbor Laboratory, One Bungtown Road, Cold Spring Harbor, NY 11724, USA. jbergmann@cshl.edu
authors: Jan H
authors: JH
authors: Bergmann
authors: Nuno M C
authors: NM
authors: Martins
authors: Vladimir
authors: V
authors: Larionov
authors: Hiroshi
authors: H
authors: Masumoto
authors: William C
authors: WC
authors: Earnshaw
mesh_terms: D001324:Autoantigens / Q000378:metabolism*; D002503:Centromere / Q000378:metabolism*; D000076247:Centromere Protein A; D051936:Centromere Protein B / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D022222:Chromosomes, Artificial, Human / Q000378:metabolism*; D004276:DNA, Satellite / Q000378:metabolism; D005822:Genetic Vectors; D006570:Heterochromatin / Q000378:metabolism; D006801:Humans; D008938:Mitosis; D009707:Nucleosomes / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D001324:Autoantigens; C000619700:CENPA protein, human; C497926:CENPB protein, human; D000076247:Centromere Protein A; D051936:Centromere Protein B; D002868:Chromosomal Proteins, Non-Histone; D004276:DNA, Satellite; D006570:Heterochromatin; D009707:Nucleosomes