| Project/Area Number |
17K07300
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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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| Research Field |
Structural biochemistry
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| Research Institution | Kitasato University (2018-2019)
University of Tsukuba (2017) |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | クロマチン / 遺伝子発現 / 転写制御 / リンカーヒストン / ヒストンシャペロン / インターフェロン / ヒストン / 転写因子 / 遺伝子 / 核酸 / 蛋白質 |
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| Outline of Final Research Achievements |
This study aimed to understand the molecular mechanism by which histone chaperones regulate gene expression program in mammalian cells. A histone chaperon NPM1 mainly localizes to the nucleoli but a fraction of NPM1 also localizes to the nucleoplasm. In this study, we found that NPM1 directly interacts with transcription factors NF-kB, STAT1, and IRF1 and regulates their target genes. In parallel, we found that NPM1 directly interacts with a linker histone-like protein HP1BP3 and regulates its chromatin binding. In this study, we demonstrated for the first time that histone chaperons directly interact with DNA binding proteins and regulate their DNA binding activity. This function of histone chaperons is suggested to contribute the regulation of gene expression program.
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| Academic Significance and Societal Importance of the Research Achievements |
NPM1は様々な固形がんで発現亢進がみられ、細胞のがん化、がんの悪性化に関わることが示唆されてきた。しかし、NPM1のどのような機能が、がん化やがんの悪性化に関わるのかは不明である。本研究より、NPM1は炎症応答性の転写因子の制御を介してがんの浸潤や転移能を促進することを見出した。本研究の成果は、がんの悪性化機構の解明につながる点で、学術的な意義、社会的な意義は大きい。本研究の成果をもとに、NPM1を標的とする分子標的薬の開発につながるように研究を発展させていきたい。
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