2021 Fiscal Year Final Research Report
Understanding of the molecular bases of liberation of germ cells from Max-dependent suppression of meiotic onset
| Project/Area Number |
19H03426
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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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| Review Section |
Basic Section 48040:Medical biochemistry-related
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| Research Institution | Saitama Medical University |
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Principal Investigator |
Akihiko Okuda 埼玉医科大学, 医学部, 教授 (60201993)
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| Co-Investigator(Kenkyū-buntansha) |
鈴木 歩 埼玉医科大学, 医学部, 講師 (80639708)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | 生殖細胞 / ES細胞 / 減数分裂 / 非典型的PRC1 / Max |
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| Outline of Final Research Achievements |
We have previously demonstrated that PRC1.6, one of non-canonical subtypes of PRC1, functions as a strong blockade against meiosis. In this study, we have unequivocally demonstrated that inactivation of the function of PRC1.6 is a prerequisite stem for germ cells to onset meiosis. Moreover, we have demonstrated that there are at least two independent mechanisms are operating in germ in parallel to attenuate repressing activity of PRC1.6 for meiotic onset. One way is that germ cells reduces expression levels of Max gene that encodes one of PRC1.6 components substantially prior to meiotic onset. The other way is that germ cells produce anomalous protein from Mga gene locus that functions as a dominant negative regular against the construction of PRC1.6 via germ cell-specific alternative splicing. In addition, we have demonstrated that both of two DNA binding domains that Mga protein bears are independently involved in repressing rather distinct sets of meiosis-related genes each other.
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| Free Research Field |
幹細胞研究
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| Academic Significance and Societal Importance of the Research Achievements |
哺乳動物の生殖細胞が体細胞分裂により活発に増殖するのを止めて減数分裂を開始する仕組みについてはほとんどわかっていない。本研究では、生殖細胞がPRC1.6複合体の機能を不活化することで減数分裂の開始を可能にしていることとの確定的な証拠を得たことに加え、PRC1.6の構成因子であるMax及びMgaをターゲットとした少なくとも2つの異なる機構により、生理的にPRC1.6の不活化が達成されていることを明らかにした。これらの成果により、減数分裂の開始機構についての研究を進展させたのみならず、男性不妊が危険因子の一つとされている精巣腫瘍の原因の解明の為の一つの基盤を提供できたと考えている。
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