2023 Fiscal Year Final Research Report
Elucidation of the replication mechanism of repression domains by Polycomb group
| Project Area | Mechanisms underlying replication of non-genomic codes that mediate plasticity and robustness for cellular inheritance |
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| Project/Area Number |
19H05745
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| Research Category |
Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
Koseki Haruhiko 国立研究開発法人理化学研究所, 生命医科学研究センター, チームリーダー (40225446)
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| Co-Investigator(Kenkyū-buntansha) |
遠藤 高帆 国立研究開発法人理化学研究所, 生命医科学研究センター, 技師 (40384862)
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| Project Period (FY) |
2019-06-28 – 2024-03-31
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| Keywords | ポリコム群 / クロマチン複製 / DNA複製 / 細胞運命決定 |
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| Outline of Final Research Achievements |
We’ve explored the links between reconstitution of nucleosome and Polycomb proteins during DNA replication by focusing on PRC1 and Enhancer of Polycomb (EpC). We revealed that in hematopoietic progenitor cells (HPCs), PCGF1-PRC1 localized in the vicinity of the replication fork to prevent aberrant accession of chromatin remodeling factors, thereby maintaing proper nucleosome densities immediately after the passage of the fork. Furthermore, by safeguarding nucleosome reconstitution, PCGF-PRC1 facilitates H3K27me3-mediated downregulation of myeloid-related genes to restrict myeloid properties in HPCs. It has been recognized that the balance between activators and repressors is critical to mediate normal differentiation and cell proliferation. Our findings highlight that this counteraction involving PCGF1-PRC1 occurs in the vicinity of the replication fork. Moreover, we also found that EpC contributed to the process of reconstitution of nucleosome.
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| Free Research Field |
発生学、遺伝学、免疫学
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| Academic Significance and Societal Importance of the Research Achievements |
従来エピジェネティックな細胞運命制御を説明するにあたり、細胞分裂時のヌクレオソーム再構築の重要性が指摘されて来たが、その証拠は十分ではなかった。当研究ではDNA複製時のクロマチン継承に関する事象が、実際に細胞運命に影響を与える事例を提示した事と、その過程で、PRC1によるクロマチンリモデリング因子の阻害作用が重要である事を示し、領域の理解を進めた事に学術的意義がある。また、DNA複製に関連したプロセスの異常が悪性疾患の発症につながることを考えると、DNA複製を介した細胞運命決定機構の理解は、悪性腫瘍の成因の理解、治療戦略の開発にも貢献する可能性があると考えられる。
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