| Project/Area Number |
23658237
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Basic veterinary science/Basic zootechnical science
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| Research Institution | The University of Tokyo |
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Principal Investigator |
OHSAKO Seiichiroh 東京大学, 医学(系)研究科(研究院), 准教授 (00274837)
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| Project Period (FY) |
2011 – 2012
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 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 |
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| Research Abstract |
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.
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