2022 Fiscal Year Final Research Report
Epigenetics from totipotency acquisition to cell differentiation during early embryogenesis
| Project/Area Number |
19H03136
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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 42030:Animal life science-related
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2023-03-31
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| Keywords | 初期胚 / エピジェネティック修飾 / 遺伝子発現 / 細胞分化 / レトロウイルルス / マウス |
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| Outline of Final Research Achievements |
In this study, we aimed to analyze the function of epigenetic modifications in the development of fertilized mouse eggs. We analyzed methylation of H3K20, H3.3R26, and H3R2 as target modifications. We also analyzed the function of Prmt6, a methyltransferase of H3R2, because it makes chimeric transcripts with MuERVL, a retrotransposon. The results revealed that monomethylation of H3K20 (H3K20me1) contributes to the genomic integrity of fertilized eggs and that methylation of H3.3R26 contributes to cell differentiation in fertilized eggs. In addition, H3R2me2a is differentially expressed among dividing cells at the 4-cell stage, and the strongly expressed dividing cells are differentiated into trophic ectoderm. Furthermore, Prmt6, a dimethyltransferase of H3R2, forms a chimeric transcript with MuERVL early in development, but not late in development. The protein produced from the chimeric transcript induces differentiation of the split cell into cells of the embryonic lineage.
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| Free Research Field |
発生生物学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、エピジェネティック修飾が初期胚の遺伝子の安定性に関与し、発生や分化を制御していることを明かにした。これらの事象を明かにすることで、受精という生命誕生の始まりから着床に至るまでの遺伝子発現がどのような分子メカニズムによって制御され、正常な発生が維持されているかを理解することができる。特に、本研究ではキメラ転写産物から作られるタンパク質が発生の時期によって本来のタンパク質とは異なる機能を持つことを世界で初めて明らかにした。これらの成果は、生殖補助医療の技術的改善にとっても貴重な情報であり、少子化対策にも大いに貢献できると考えられる。
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