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

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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.