| Project/Area Number |
16H04817
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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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| Research Field |
Genetics/Chromosome dynamics
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| Research Institution | Nagoya University |
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Principal Investigator |
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| Research Collaborator |
Inoue Kota
Shimosuga Ken-ichi
Sugimoto Hirotaka
Fukuda Kei
Glinka Michael
Kawase Masaki
Ichiyanagi Tomoko
Sasaki Hiroyuki
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2018: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
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| Keywords | レトロトランスポゾン / エピジェネティクス / 哺乳類 / 生殖細胞 / DNAメチル化 / piRNA |
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| Outline of Final Research Achievements |
Regulation of the transposable activity of millions of copies of retrotransposons is important for maintaining the genomic integrity. We have revealed that DNA methylation is an important epigenetic modification to transcriptionally silence the retrotransposons and that piRNAs play an important role in post-transcriptional silencing of retrotransposons. Interestingly, in the early stage of germ cell development (prospermatogonia), piRNAs play a dominant role, whereas DNA methylation becomes more important in the later stage (spermatocytes). We investigated retrotransposon expression by strand-specific mRNA-seq of prospermatogonia, spermatogonia, and spermatocytes of wild-type, Dnmt3L, and Pld6 mutant mice. The results showed that the shift from the piRNA-centered to DNA methylation-centered regulatory systems occurs gradually during development. Moreover, ChIP-seq analysis of spermatogonia revealed that H3K9me3 modification at retrotransposons depends on DNA methylation.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究によって、レトロトランスポゾン制御機構はある時点で転換するというよりは、徐々に変化していくことが明らかになった。したがって、レトロトランスポゾンを取り巻くクロマチン状況も徐々に経時的に変化していくものと思われる。今後は、そのクロマチン修飾の経時変化をとらえる必要がある。さらに、本研究からはもう一つ重要な発見が得られた。それは、DNAメチル化によってヒストン修飾が影響を受けうるということである。ヒストンのメチル化がDNAのメチル化に影響を与える例は多くても、その逆は報告がなく、新しいエピジェネティック制御の相互作用のあり方である。
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