2022 Fiscal Year Final Research Report
Heterochromatin dysfunction and its related diseases induced by impaired DNA demethylation
Project/Area Number |
20KK0351
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Research Category |
Fund for the Promotion of Joint International Research (Fostering Joint International Research (A))
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 49070:Immunology-related
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Research Institution | Chiba University |
Principal Investigator |
ONODERA Atsushi 千葉大学, 大学院医学研究院, 准教授 (10586598)
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Project Period (FY) |
2021 – 2022
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Keywords | エピジェネティクス / 発生・分化 / 第三世代シークエンス / 炎症性疾患 / 発現制御 |
Outline of Final Research Achievements |
We analyzed the association between elevated RNA transposon expression due to heterochromatin dysfunction and the leukemogenesis by using TET-deficient mice as a model. Experimental data were obtained at the La Jolla Institute for Immunology, the main collaborating overseas research institute. Data analysis was supported by University of California, San Diego. As a result of our research, we found a region where heterochromatin was switched to euchromatin by TET deficiency, and RNA transposon expression was induced. The region encodes the Stefin gene cluster, whose human homolog gene expression levels were well-correlated with cancer patients’ prognosis. These findings indicate that heterochromatin dysfunction potentially leads to leukemogenesis through upregulation of RNA transposons.
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Free Research Field |
免疫学とエピジェネティクスおよびその融合分野
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Academic Significance and Societal Importance of the Research Achievements |
ヘテロクロマチン機能不全と疾患発症の関係性を明らかにした報告は少なく、本研究で発表した論文は両者の関係を裏付ける学術的に大きな成果であった。また、ヘテロクロマチンが機能不全を起こす領域にクラスターを形成するStefin遺伝子のヒトにおけるホモログ遺伝子群の高発現は、がん患者の予後に悪影響を与えることが分かった。これらの知見は、Stefin遺伝子群の発現が、がん患者の予後や治療感受性を予測できるバイオマーカーとして使える可能性を示唆し、社会的意義のある研究成果であると言える。
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