Involvement of bivalent histone modification in age-specific cancer susceptibility

Research Project

Project/Area Number	15K18420
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Tumor biology
Research Institution	National Cancer Center Japan
Principal Investigator	Hattori Naoko 国立研究開発法人国立がん研究センター, 研究所, 研究員 (30611090)
Project Period (FY)	2015-04-01 – 2017-03-31
Project Status	Completed (Fiscal Year 2016)
Budget Amount *help	¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000) Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000) Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords	エピジェネティクス / ヒストン修飾 / 乳腺発がん / Bivalentヒストン修飾 / 発がん感受性 / bivalentヒストン修飾
Outline of Final Research Achievements	To reveal the molecular mechanism of age-specific cancer susceptibility of mammary glands, I investigated the involvement of bivalent histone modification. ChIP-chip analysis of H3K4me3 and H3K27me3 using rat mammary epithelial cells showed that 91 genes were identified as the bivalent genes in sensitive period. Among the 91 genes, 7 genes were methylated in rat mammary carcinomas, and 4 genes did not express in normal mammary epithelial cells. The human homolog of one gene was known as a tumor suppressor gene that is methylation-silenced in breast cancer. I identified the sensitive period-specific bivalent genes in mammary gland, which were methylated in mammary carcinoma, suggesting that bivalent modification might be a seed of DNA methylation during carcinogenesis.