title: Toxicity of nickel compounds mediated by HTZ1, histone variant H2A.Z, in Saccharomyces cerevisiae.
abstract: Nickel compounds have toxic and carcinogenic effects. Several cellular targets have been identified and the toxicity is thought to be mediated by genetic and epigenetic factors. Gene expression from chromatin is regulated by posttranslational histone modifications, ATP-dependent chromatin remodeling, and the incorporation of histone variants. Nickel compounds decrease acetylation levels of all four histones and increase ubiquitylation of H2A and H2B and dimethylation of H3 lysine 9. Less attention has been focused on histone variants in nickel toxicity. Here we demonstrate that a null mutation of H2A.Z (HTZ1 in Saccharomyces cerevisiae), a variant of H2A, decreases the sensitivity to soluble nickel compounds. In addition, we show that a mutation in the acetylatable residues in Htz1p does not alter the sensitivity to nickel compounds. Furthermore, sensitivity to nickel compounds of the null mutant of SWR1 encoding the catalytic subunit of the ATP-dependent chromatin remodeling complex that specifically loads Htz1p into chromatin, was identical to that of the htz1 mutant. Taken together, these results reveal that the incorporation into chromatin, but not acetylation, of Htz1p is important to the toxicity of nickel compounds.
authors.affiliation: Department of Molecular Biology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Aichi, Japan. osada@phar.nagoya-cu.ac.jp
authors.forename: Shigehiro
authors.initials: S
authors.lastname: Osada
authors.forename: Urara
authors.initials: U
authors.lastname: Gomita
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Imagawa
mesh_terms: D000107:Acetylation; D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D006657:Histones / Q000235:genetics / Q000502:physiology*; D008239:Lysine / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009532:Nickel / Q000633:toxicity*; D010957:Plasmids; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D002843:Chromatin; D006657:Histones; C493530:Htz1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C022838:nickel chloride; D009532:Nickel; D000251:Adenosine Triphosphatases; C481261:Swr1 protein, S cerevisiae; D008239:Lysine