| Project/Area Number |
18K05316
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 37010:Bio-related chemistry
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| Research Institution | Osaka University |
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Principal Investigator |
Kawakami Toru 大阪大学, 蛋白質研究所, 准教授 (70273711)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 蛋白質 / ライゲーション / ヒストン / 翻訳後修飾 / ユビキチン / DNAメチル化 / ヌクレオソーム |
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| Outline of Final Research Achievements |
Based on the peptide ligation method, we decided to chemically synthesize four types of histones, including post-translational modifications, with the aim of constructing nucleosomes containing selectively modified histones. We also attempt to develop a more efficient ligation method. As a result, we synthesized three types of histones including post-translational modifications, including the results so far. In particular, we succeeded in synthesizing histones containing ubiquitin modification, which is a small protein, and found that the modification activates DNA methyltransferase. Although the synthesis of one type of histone could not be started, it can be synthesized by the similar strategy. We have also found a ligation method with high reaction efficiency and are studying its application.
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| Academic Significance and Societal Importance of the Research Achievements |
遺伝子（DNA）は4種類のヒストンタンパク質からなる8量体に巻き付きヌクレオソームを構成する．これが連なった状態で細胞核に収納される．ヒストンやその関連タンパク質は種々の翻訳後修飾（化学修飾）を受けることで，構造変化やタンパク質間の相互作用を調整して，この遺伝子の発現制御を行っている．これらの修飾は非常に複雑であり，その機能は必ずしも解明されていない．これらの翻訳後修飾を受けたヒストンを選択的に化学合成できるようになれば，それらの機能の解明に非常に有用である．
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