Epigenetic mutagen as histone modulator can be detected by yeast flocculation
| Autor: | Masatomi Shimizu, Masamitsu Honma, Kei-ichi Sugiyama, Hiroko Furusawa, Petr Grúz |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
DNA (Cytosine-5-)-Methyltransferase 1
0301 basic medicine Saccharomyces cerevisiae Proteins medicine.drug_class Health Toxicology and Mutagenesis Anthraquinones Saccharomyces cerevisiae Hydroxamic Acids Toxicology Epigenesis Genetic Histones 03 medical and health sciences Histone H3 0302 clinical medicine Gene Expression Regulation Fungal Yeast flocculation Genetics medicine Nucleosome DNA (Cytosine-5-)-Methyltransferases Epigenetics Genetics (clinical) biology Mutagenicity Tests Histone deacetylase inhibitor DNA Methylation Up-Regulation Mannose-Binding Lectins 030104 developmental biology Histone Trichostatin A Biochemistry 030220 oncology & carcinogenesis DNA methylation biology.protein sense organs Mutagens medicine.drug |
| Zdroj: | Mutagenesis. 31:687-693 |
| ISSN: | 1464-3804 0267-8357 |
| DOI: | 10.1093/mutage/gew041 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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