title: HJURP is involved in the expansion of centromeric chromatin.
abstract: The CENP-A-specific chaperone HJURP mediates CENP-A deposition at centromeres. The N-terminal region of HJURP is responsible for binding to soluble CENP-A. However, it is unclear whether other regions of HJURP have additional functions for centromere formation and maintenance. In this study, we generated chicken DT40 knockout cell lines and gene replacement constructs for HJURP to assess the additional functions of HJURP in vivo. Our analysis revealed that the middle region of HJURP associates with the Mis18 complex protein M18BP1/KNL2 and that the HJURP-M18BP1 association is required for HJURP function. In addition, on the basis of the analysis of artificial centromeres induced by ectopic HJURP localization, we demonstrate that HJURP exhibits a centromere expansion activity that is separable from its CENP-A-binding activity. We also observed centromere expansion surrounding natural centromeres after HJURP overexpression. We propose that this centromere expansion activity reflects the functional properties of HJURP, which uses this activity to contribute to the plastic establishment of a centromeric chromatin structure.
authors.affiliation: Department of Molecular Genetics, National Institute of Genetics, and Graduate University for Advanced Studies (SOKENDAI), Mishima, Shizuoka 411-8540, Japan.
authors.forename: Marinela
authors.initials: M
authors.lastname: Perpelescu
authors.affiliation: Department of Molecular Genetics, National Institute of Genetics, and Graduate University for Advanced Studies (SOKENDAI), Mishima, Shizuoka 411-8540, Japan Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hori
authors.affiliation: Comparative Genomics Laboratory, National Institute of Genetics, Mishima, Shizuoka 411-8540, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Toyoda
authors.affiliation: Cell Innovation Project, National Institute of Genetics, Mishima, Shizuoka 411-8540, Japan.
authors.forename: Sadahiko
authors.initials: S
authors.lastname: Misu
authors.affiliation: Cell Innovation Project, National Institute of Genetics, Mishima, Shizuoka 411-8540, Japan.
authors.forename: Norikazu
authors.initials: N
authors.lastname: Monma
authors.affiliation: Cell Innovation Project, National Institute of Genetics, Mishima, Shizuoka 411-8540, Japan.
authors.forename: Kazuho
authors.initials: K
authors.lastname: Ikeo
authors.affiliation: Graduate School of Life Science, Hokkaido University, Sapporo. 001-0021, Japan.
authors.forename: Chikashi
authors.initials: C
authors.lastname: Obuse
authors.affiliation: Comparative Genomics Laboratory, National Institute of Genetics, Mishima, Shizuoka 411-8540, Japan National Institute of Informatics, Hitotsubashi, Chiyoda-ku, Tokyo 101-8430, Japan.
authors.forename: Asao
authors.initials: A
authors.lastname: Fujiyama
authors.affiliation: Department of Molecular Genetics, National Institute of Genetics, and Graduate University for Advanced Studies (SOKENDAI), Mishima, Shizuoka 411-8540, Japan Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan tfukagawa@fbs.osaka-u.ac.jp.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Fukagawa
mesh_terms: D001324:Autoantigens / Q000378:metabolism; D002460:Cell Line; D002503:Centromere / Q000378:metabolism*; D000076247:Centromere Protein A; D002843:Chromatin / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D018832:Molecular Chaperones; D017434:Protein Structure, Tertiary
chemical_list: D001324:Autoantigens; C000619700:CENPA protein, human; D000076247:Centromere Protein A; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C524371:HJURP protein, human; D006657:Histones; D018832:Molecular Chaperones