Molecular mechanism of programing of the adaptation to environment: search for the epigenomic modification alteration in the germ line

环境适应编程的分子机制：寻找种系中的表观基因组修饰改变

• 批准号: 23658237
• 负责人: OHSAKO Seiichiroh
• 金额: $ 2.5万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-23658237/
• 关键词: エピジェネティクス; 化学物質; 後世代影響; メチル化; 生殖細胞; 進化; 肝臓; 薬物代謝酵素

As a preliminary experiment, epigenomes of the male offspring born form the non-exposed females mated to F1 males exposed to dioxin (TCDD) during fetal stage. The methylation frequency of CpG of Cyp1a1 promoter region located on -500 of transcription start site of exposed animals was similar with that of the control in an epididymis sperm, liver, and kidney. Thus, it was suggested that trans-generational effects were not obtained. Next, hypomethylation was examined in the hepatoma Hep1c1c7 cells, but any methylation were not observed in CpGs of Cyp1a1 promoter region. Therefore we decided to focus on the hypomethylation of the liver in the C57BL/6J F1 mice exposed TCDD on E12.5. Hypomethylation of CpG was found to begin to occur from birth day 3 in the liver. Using these neonatal liver samples, ChIP assay with three types of DNA methyl-transferases were carried out. The binding of Dnmt1 and Dnmt3b to Cyp1a1 promoter region was found to significantly decrease by TCDD exposure.

作为初步实验，未暴露雌性与暴露于二恶英（TCDD）的F1雄性在胎儿期交配所生雄性后代的表观基因组。在附睾精子、肝脏和肾脏中，暴露动物Cyp 1a 1启动子区位于转录起始位点-500的CpG甲基化频率与对照组相似。因此，有人认为，没有产生跨代效应。接下来，在肝癌Hep 1c 1c 7细胞中检测到低甲基化，但在Cyp 1a 1启动子区域的CpG中未观察到任何甲基化。因此，我们决定将重点放在C57 BL/6 J F1小鼠暴露于TCDD的E12.5肝脏的低甲基化。发现CpG的低甲基化从出生第3天起在肝脏中开始发生。使用这些新生儿肝脏样品，用三种类型的DNA甲基转移酶进行ChIP测定。Dnmt 1和Dnmt 3b与Cyp 1a 1启动子区的结合被发现显着降低TCDD暴露。

项目成果

Effects of Ahr agonist on neuronal cell differentiation from human ES cells.

Ahr 激动剂对人 ES 细胞分化为神经元细胞的影响。

• 发表时间: 2012
• 作者: Seiichiroh Ohsako;Junko Yamane;Satoshi Imanishi;Chiharu Tohyama
• 通讯作者: Chiharu Tohyama

環境汚染化学物質の周産期曝露による表現型変化―エピジェネティクスと環境毒性学―

围产期暴露于环境污染物导致的表型变化 - 表观遗传学和环境毒理学 -

• 发表时间: 2012
• 作者: Iwami;S.;大迫誠一郎
• 通讯作者: 大迫誠一郎

Generation of the human ES cell line driven by dioxin responsive reporter gene

二恶英响应报告基因驱动的人类 ES 细胞系的产生

• 发表时间: 2013
• 作者: Otsuki;H.;Hishiki;T.;Miura;T.;Hashimoto;C.;Narumi;T.;Tamamura;H.;Yoshimura;K.;Matsushita;S.;and Igarashi;T.;辰巳隆一;Seiichiroh Ohsako
• 通讯作者: Seiichiroh Ohsako

Critical role of microsomal prostaglandin E synthase-1 in the hydronephrosis caused by lactational exposure to dioxin in mice

微粒体前列腺素E合酶1在小鼠哺乳期接触二恶英引起的肾积水中的关键作用

• DOI: 10.1093/toxsci/kfs115
• 发表时间: 2012
• 期刊: Toxicol. Sci
• 作者: Yoshioka W;Aida-Yasuoka K;Fujisawa N;Kawaguchi T;Ohsako S;Hara S;Uematsu S;Akira S;Tohyama C
• 通讯作者: Tohyama C

Perinatal Exposure to Environmental Chemicals Induces Epigenomic Changes in Offspring

围产期接触环境化学物质会引起后代表观基因组变化

• DOI: 10.3123/jemsge.33.43
• 发表时间: 2011
• 期刊: Genes and Environment
• 影响因子: 1.7
• 作者: Fujita;Y.;Otsuki;H.;Watanabe;Y.;Yasui;M.;Kobayashi;T.;Miura;T.;and Igarashi;T;Ohsako S
• 通讯作者: Ohsako S