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2023 Fiscal Year Final Research Report

PCGF1-PRC1 in the vicinity of thr fork safeguards multipotency of hematopoietic progenitor cells

Research Project

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Project/Area Number 21K16257
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 54010:Hematology and medical oncology-related
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

Takano Junichiro  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, 特別研究員 (00852162)

Project Period (FY) 2021-04-01 – 2024-03-31
Keywordsポリコム群タンパク / ヌクレオソーム / DNA複製 / ヒストン再構築 / 造血系 / 細胞運命決定
Outline of Final Research Achievements

We’ve explored the mechanisms regulating the reconstitution of nucleosome during DNA replication and their roles in cell fate determination. We revealed that in hematopoietic progenitor cells (HPCs), PCGF1-PRC1 localized in the vicinity of the replication fork to prevent aberrant over-loading of chromatin remodeling factors, thereby PCGF1-PRC1 maintains proper nucleosome densities immediately after the passage of the fork to optimize reconstitution of nucleosomes. Furthermore, by regulating nucleosome configurations at the replication fork, 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 to stabilize nucleosome conformation and cell fate determination.

Free Research Field

エピジェネティクス

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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Published: 2025-01-30  

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