| Project/Area Number |
16H04747
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Molecular biology
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| Research Institution | Kazusa DNA Research Institute |
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Principal Investigator |
Masumoto Hiroshi 公益財団法人かずさDNA研究所, 先端研究開発部, 室長 (70229384)
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| Research Collaborator |
Okazaki Kouei
Ohzeki Junichirou
Kugou Kazuto
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2018: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2017: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
Fiscal Year 2016: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
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| Keywords | セントロメア / ヘテロクロマチン / 人工染色体 / CENP-A / ヒストン交換 / クロマチン / 反復DNA |
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| Outline of Final Research Achievements |
On a human artificial chromosome (HAC), various functional chromatins are newly assembled and maintained as an autonomous extra chromosome. In this study, we aimed to elucidate mechanism of the balance control between functional centromere formation and heterochromatin assembly using HAC system composed of synthetic repetitive DNAs. We have revealed that histone acetyl transferase (KAT7) is recruited by the Mis18 complex which is essential for the centromere chromatin assembly, and is also involved in the assembly balance and functional maintenance between centromere and heterochromatin. Furthermore, by combining various synthetic repetitive DNAs, we have developed next-generation HACs that can regulate the assembly balance of both chromatins, and have significantly improved the artificial chromosome formation activity which had been reduced with a single synthetic repetitive DNA.
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| Academic Significance and Societal Importance of the Research Achievements |
染色体機能制御の乱れは、細胞死や老化、異常増殖を引き起こすが、その詳細は未解明のままである。ヒト人工染色体では、細胞へ導入した裸のDNA上に機能するクロマチンが新規形成され、染色体として自律的に維持される。 本研究では、このヒト人工染色体と構成学的手法を組み合わせ、染色体分配に関わるセントロメア機能形成とヘテロクロマチン集合のバランス調節機構の解明を進めた。本研究により染色体分配機構の異常へ繋がるメカニズムの解明が進み細胞死や老化、異常増殖への原因解明が期待される。次世代型人工染色体の開発は遺伝子治療や物質生産を目指した巨大DNA断片導入用ベクターとしても高い利用価値が見込まれる。
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