| Project/Area Number |
17H06564
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
Medical genome science
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| Research Institution | Chiba University |
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Principal Investigator |
Namba Hiroe 千葉大学, 大学院医学研究院, 特任助教 (10799654)
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| Research Collaborator |
KANEDA Atsushi
OHARA Osamu
MATSUSAKA Keisuke
OKABE Atsushi
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| Project Period (FY) |
2017-08-25 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 癌エピゲノム / Epstein-Barr virus / TET / DNAメチル化 / Epstein-Barrウイルス / 胃癌 / Epstein-Barr ウイルス / ヒドロキシメチル化 / 癌エピジェネティクス |
|---|
| Outline of Final Research Achievements |
Epstein-Barr virus (EBV) positive gastric cancer shows the most extensive DNA methylation among all human malignancies. One of the DNA demethylases, TET2, is repressed by EBV infection. In this study, TET2 overexpressing cells were successfully infected with EBV. Regarding TET2 targeting genes, induction of DNA methylation was partially inhibited, and histone activating marks were upregulated compared to normal EBV infection without TET2 overexpression, accompanied by upregulation of targeting genes. Furthermore, we confirmed proteins on SDS-PAGE gel that may work with TET2 for histone modification changes. We have made knockdown cell lines of those protein candidates, and conducted histone modification analysis by ChIP-seq and compared to those of TET2 knockdown cell line. Some regions with histone active marks downregulated were overlapped.
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| Academic Significance and Societal Importance of the Research Achievements |
遺伝子発現を制御するDNAメチル化やヒストン修飾などのエピジェネティクスは、生物の発生はもちろん癌をはじめとする多くの病気の発生に関わる。短期間でダイナミックなエピゲノム変化を生理的に生じさせることが可能なEBウイルス感染モデルを用いることにより、エピゲノム変化の誘導分子機構を詳細に解析することが可能となり、薬剤開発や診断方法の確立等幅広く医学生物学に貢献する。
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