title: Mammal-specific H2A variant, H2ABbd, is involved in apoptotic induction via activation of NF-κB signaling pathway.
abstract: Histone variants play specific roles in maintenance and regulation of chromatin structures. H2ABbd, an H2A variant, possesses a highly divergent structure compared with canonical H2A and is highly expressed in postmeiotic germ cells, but its functions in the regulation of gene expression are largely unknown. In the present study, we investigated the cellular phenotype associated with enforced H2ABbd expression. Among H2A variants, H2ABbd specifically caused growth defect in human cells and induced apoptosis. H2ABbd expression resulted in degradation of inhibitor of κB-α and translocation of NF-κB into nuclei, indicating the activation of NF-κB. Intriguingly, NF-κB activity was essential for H2ABbd-induced apoptosis. H2ABbd overexpression resulted in DNA damage after release from G1/S, progressed through the S phase slowly, and induced apoptosis. Furthermore, gene expression microarray analysis revealed that expression of H2ABbd activates groups of genes involved in apoptosis and postmeiotic germ cell development, suggesting that H2ABbd might influence transcription. Taken together, our data suggest that H2ABbd may contribute to specific chromatin structures and promote NF-κB activation, which could in turn induce apoptosis in mammalian cells.
authors.affiliation: Department of Cell Biology, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Goshima
authors.affiliation: Department of Cell Biology, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan. Electronic address: midorism@med.nagoya-cu.ac.jp.
authors.forename: Midori
authors.initials: M
authors.lastname: Shimada
authors.affiliation: Development Genetics Group, RIKEN Center for Integrative Medical Sciences (IMS), 1-7-22 Suehiuro-cho, Tsurumi, Yokohama, Kanagawa 230-0045, Japan.
authors.forename: Jafar
authors.initials: J
authors.lastname: Sharif
authors.affiliation: Department of Cell Biology, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Matsuo
authors.affiliation: Department of Cell Biology, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
authors.forename: Toshinori
authors.initials: T
authors.lastname: Misaki
authors.affiliation: Department of Cell Biology, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Johmura
authors.affiliation: Department of Cell Biology, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Murata
authors.affiliation: Development Genetics Group, RIKEN Center for Integrative Medical Sciences (IMS), 1-7-22 Suehiuro-cho, Tsurumi, Yokohama, Kanagawa 230-0045, Japan.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Koseki
authors.affiliation: Department of Cell Biology, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan. Electronic address: mkt-naka@med.nagoya-cu.ac.jp.
authors.forename: Makoto
authors.initials: M
authors.lastname: Nakanishi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D004261:DNA Replication; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D017931:DNA Primers; D006657:Histones; D016328:NF-kappa B
keywords: Apoptosis; Cell Cycle; Chromatin Histone Modification; DNA Damage; Gene Expression; Histones