title: CENP-C recruits M18BP1 to centromeres to promote CENP-A chromatin assembly.
abstract: Eukaryotic chromosomes segregate by attaching to microtubules of the mitotic spindle through a chromosomal microtubule binding site called the kinetochore. Kinetochores assemble on a specialized chromosomal locus termed the centromere, which is characterized by the replacement of histone H3 in centromeric nucleosomes with the essential histone H3 variant CENP-A (centromere protein A). Understanding how CENP-A chromatin is assembled and maintained is central to understanding chromosome segregation mechanisms. CENP-A nucleosome assembly requires the Mis18 complex and the CENP-A chaperone HJURP. These factors localize to centromeres in telophase/G1, when new CENP-A chromatin is assembled. The mechanisms that control their targeting are unknown. In this paper, we identify a mechanism for recruiting the Mis18 complex protein M18BP1 to centromeres. We show that depletion of CENP-C prevents M18BP1 targeting to metaphase centromeres and inhibits CENP-A chromatin assembly. We find that M18BP1 directly binds CENP-C through conserved domains in the CENP-C protein. Thus, CENP-C provides a link between existing CENP-A chromatin and the proteins required for new CENP-A nucleosome assembly.
authors.affiliation: Department of Biochemistry, Stanford University Medical School, Stanford, CA 94305, USA.
authors.forename: Ben
authors.initials: B
authors.lastname: Moree
authors.forename: Corey B
authors.initials: CB
authors.lastname: Meyer
authors.forename: Colin J
authors.initials: CJ
authors.lastname: Fuller
authors.forename: Aaron F
authors.initials: AF
authors.lastname: Straight
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002503:Centromere / Q000378:metabolism; D000076247:Centromere Protein A; D002843:Chromatin / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D009707:Nucleosomes / Q000378:metabolism; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D001324:Autoantigens; D002352:Carrier Proteins; D000076247:Centromere Protein A; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C557677:Holliday junction recognizing protein, Xenopus; C562324:M18BP1 protein, Xenopus; D009707:Nucleosomes; D029867:Xenopus Proteins; C060905:centromere protein C