title: RbAp48 is essential for viability of vertebrate cells and plays a role in chromosome stability.
abstract: RbAp46/48, histone chaperone, is a family of evolutionarily conserved WD40 repeat-containing proteins, which are involved in various chromatin-metabolizing processes, but their in vivo functional relevance is yet unclear. In order to examine the biological role of pRbAp48 in chicken DT40 cells, we generated a tetracycline-inducible system for conditional RbAp48-knockout cells. Depletion of RbAp48 led to delayed S phase progression associated with slow DNA synthesis and nascent nucleosome formation, followed by accumulation in G2/M phase, finally leading to cell death. Prior to cell death, these cells exhibited aberrant mitosis such as highly condensed and abnormal chromosome alignment on the metaphase plate, leading to chromosome missegregation. Depletion of RbAp48 also caused dissociation of heterochromatin protein 1 (HP1) from pericentromeric heterochromatin. Furthermore, depletion of RbAp48 from cells led to elevated levels of acetylation and slightly decreased levels of methylation, specifically at Lys-9 residue of histone H3. These results suggest that RbAp48 plays an important role in chromosome stability for proper organization of heterochromatin structure through the regulation of epigenetic mark.
authors.affiliation: Section of Biochemistry and Molecular Biology, Department of Medical Sciences, University of Miyazaki, 5200, Kihara, Kiyotake, Miyazaki, 889-1692, Japan.
authors.forename: Pasjan
authors.initials: P
authors.lastname: Satrimafitrah
authors.affiliation: Section of Biochemistry and Molecular Biology, Department of Medical Sciences, University of Miyazaki, 5200, Kihara, Kiyotake, Miyazaki, 889-1692, Japan.|Fish Genetics & Biotechnology Division, Central Institute of Freshwater Aquaculture, Indian Council of Agricultural Research, Kausalyaganga, Bhubaneswar, 751002, Odisha, India.
authors.forename: Hirak Kumar
authors.initials: HK
authors.lastname: Barman
authors.affiliation: Section of Biochemistry and Molecular Biology, Department of Medical Sciences, University of Miyazaki, 5200, Kihara, Kiyotake, Miyazaki, 889-1692, Japan.|Department of Chemistry, Hasanuddin University, Makassar, 90245, Indonesia.
authors.forename: Ahyar
authors.initials: A
authors.lastname: Ahmad
authors.affiliation: Section of Biochemistry and Molecular Biology, Department of Medical Sciences, University of Miyazaki, 5200, Kihara, Kiyotake, Miyazaki, 889-1692, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Nishitoh
authors.affiliation: Section of Biochemistry and Molecular Biology, Department of Medical Sciences, University of Miyazaki, 5200, Kihara, Kiyotake, Miyazaki, 889-1692, Japan.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Nakayama
authors.affiliation: Department of Molecular Genetics, National Institute of Genetics, Mishima, Shizuoka, 411-8540, Japan.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Fukagawa
authors.affiliation: Section of Biochemistry and Molecular Biology, Department of Medical Sciences, University of Miyazaki, 5200, Kihara, Kiyotake, Miyazaki, 889-1692, Japan. ytakami@med.miyazaki-u.ac.jp.
authors.forename: Yasunari
authors.initials: Y
authors.lastname: Takami
mesh_terms: D000107:Acetylation; D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000235:genetics*; D002645:Chickens / Q000235:genetics*; D000090266:Chromobox Protein Homolog 5; D043171:Chromosomal Instability / Q000235:genetics*; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D016195:G2 Phase / Q000235:genetics; D055786:Gene Knockout Techniques; D006570:Heterochromatin / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D008745:Methylation; D056505:Retinoblastoma-Binding Protein 4 / Q000235:genetics* / Q000378:metabolism; D016196:S Phase / Q000235:genetics
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D006570:Heterochromatin; D006657:Histones; D056505:Retinoblastoma-Binding Protein 4; D000090266:Chromobox Protein Homolog 5
keywords: Chromatin assembly; Heterochromatin; Histone chaperone; Histone modification; WD40 protein