2023 Fiscal Year Final Research Report
Analysis of higher order chromatin structure in embryonic macrophage differentiation
Project/Area Number |
21K20778
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Research Category |
Grant-in-Aid for Research Activity Start-up
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Allocation Type | Multi-year Fund |
Review Section |
0803:Pathology, infection/immunology, and related fields
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Research Institution | Kumamoto University |
Principal Investigator |
Kikuchi Kenta 熊本大学, 国際先端医学研究機構, 特別研究員(PD) (60907939)
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Project Period (FY) |
2021-08-30 – 2023-03-31
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Keywords | クロマチン高次構造 / マクロファージ / 分化 / 機能 |
Outline of Final Research Achievements |
Mononuclear phagocytes, including macrophages, are functionally diverse. However, molecular mechanisms underlying such differences remain unclear. In this study, we analyzed the changes in the higher-order chromatin structures of mononuclear phagocytes during differentiation. We found that higher-order chromatin structures including nuclear compartments and topologically associating domains in the regions of mononuclear phagocyte lineage-specific genes are reorganized during differentiation. Furthermore, some of these structures are regulated by lineage-specific transcription factors. We analyze how the established higher-order chromatin structures are involved in gene regulation.
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Free Research Field |
免疫学
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Academic Significance and Societal Importance of the Research Achievements |
マクロファージを含む単核貪食細胞は全身に分布し、極めて多様な役割があり、疾患発症にも関与する。単核貪食細胞の性質に発生経路の違いが与える影響については未だ結論がでておらず、この分野における重要な問題点である。本研究では、系譜特異的遺伝子領域におけるクロマチン高次構造の事前形成が単核貪食細胞の機能発現に重要であることを示した。この知見は、細胞のクロマチン高次構造を解析し、構造形成に関与する転写因子やクロマチン制御因子を同定することが、機能を制御する根幹のメカニズム解明につながることを示唆する。単核貪食細胞の形質決定に重要な分子を同定できれば、疾患の新規治療法の開発に貢献できる可能性がある。
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