title: Epigenetic mutagen as histone modulator can be detected by yeast flocculation.
abstract: We have previously reported that flocculation of a yeast co-transformed with the human DNA methyltransferase 1 (DNMT1) and DNMT3B genes was inhibited by DNMT inhibitors. It is well known that epigenetic mutagens can disturb nucleosome positioning via DNA methylation and/or histone modification. In this study we first examined the effects of trichostatin A (TSA), a histone deacetylase inhibitor, on the flocculation level of yeast. TSA dose-dependently promoted the flocculation exhibited by the yeast transformed with the DNMT genes or empty vectors. Furthermore, TSA induced the expression of the flocculin-encoding gene FLO1 The anthracene-derived alizarin, a natural madder root dye, has a potential for carcinogenesis promotion; however, the mode of action has not been elucidated. It is considered that epigenetic changes can promote cancer. Alizarin but not anthracene enhanced the flocculation level of the yeast. Similar to TSA, alizarin also upregulated FLO1 mRNA. Surprisingly, western blotting indicated that alizarin, but not anthracene, reduced the level of histone H3 in yeast, and alizarin-treated cells frequently displayed abnormally shaped nuclei. These findings suggest that alizarin uniquely influences nucleosome structure. Taken together with our previous findings, this study suggests that the DNMT gene-transformed yeast strains are a useful tool for screening various classes of epigenetic mutagens.
authors.affiliation: Division of Genetics and Mutagenesis, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan, sugiyama@nihs.go.jp.
authors.forename: Kei-Ichi
authors.initials: KI
authors.lastname: Sugiyama
authors.affiliation: Division of Genetics and Mutagenesis, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Furusawa
authors.affiliation: Division of Genetics and Mutagenesis, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.|Division of Medical Nutrition, Faculty of Healthcare, Tokyo Healthcare University, 3-11-3 Setagaya, Setagaya-ku, Tokyo 154-8568, Japan.
authors.forename: Masatomi
authors.initials: M
authors.lastname: Shimizu
authors.affiliation: Division of Genetics and Mutagenesis, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
authors.forename: Petr
authors.initials: P
authors.lastname: Grúz
authors.affiliation: Division of Genetics and Mutagenesis, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Honma
mesh_terms: D000880:Anthraquinones / Q000494:pharmacology* / Q000633:toxicity; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019175:DNA Methylation; D044127:Epigenesis, Genetic / Q000187:drug effects*; D015966:Gene Expression Regulation, Fungal; D006657:Histones / Q000378:metabolism; D006877:Hydroxamic Acids / Q000494:pharmacology / Q000633:toxicity; D037241:Mannose-Binding Lectins / Q000235:genetics*; D009152:Mutagenicity Tests / Q000379:methods*; D009153:Mutagens / Q000494:pharmacology / Q000633:toxicity; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D000880:Anthraquinones; C087578:FLO1 protein, S cerevisiae; D006657:Histones; D006877:Hydroxamic Acids; D037241:Mannose-Binding Lectins; D009153:Mutagens; D029701:Saccharomyces cerevisiae Proteins; C012589:trichostatin A; C010078:alizarin; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human