2022 Fiscal Year Final Research Report
Elucidation of commonalities and specificities in genomic imprinting inheritance by novel mechanisms
| Project/Area Number |
19H03134
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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 | University of Tsukuba |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2023-03-31
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| Keywords | ゲノム刷り込み / 遺伝子改変マウス / 制御分子 |
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| Outline of Final Research Achievements |
The objective of this study is to understand the molecular mechanism of "genomic imprinting”, an epigenetic phenomenon unique to placental mammals, through elucidation of the “postfertilization imprinted methylation activity”, which we originally discovered. During the project period, we identified several proteins (binding activities) bound to the 118bp sequence of the H19 ICR by gel shift assay, which is essential for the phenomenon, and generated transgenic mice carrying mutations in the cis-binding motifs to verify their functions (3 conference presentations and one manuscript in preparation). In addition, by generating transgenic mice, the conservation of post-fertilization imprinted methylation phenomena in human and rat H19 ICR and other DMRs (IG-DMR) was demonstrated (5 conference presentations, one paper published).
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| Free Research Field |
動物生命科学
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| Academic Significance and Societal Importance of the Research Achievements |
学術的意義：DNA塩基配列に依存しない遺伝様式であるエピジェネティクスにおいて、その情報の担い手はDNAメチル化やヒストン修飾であり、これらは細胞分裂や世代を超えて継承される。ゲノム刷り込みでは、生殖細胞でのDNAメチル化が、受精後に両アレルを区別するためのマークと考えられているが、我々の成果は、新規マークの存在を示唆する。
社会的意義：ゲノム刷り込み異常が関わるエピジェネティクス疾患の原因として、生殖細胞での確立、あるいは、着床後の維持過程における刷り込みメチル化の破綻がある。我々の成果は、受精直後の維持過程でも破綻が生じうることを示唆し、関与する分子の同定により、治療や診断が可能となる。
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