2013 Fiscal Year Annual Research Report
母性因子による胚性ゲノム活性化のエピジェネティクス解析
Project/Area Number |
23380164
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Research Institution | Kyoto University |
Principal Investigator |
南 直治郎 京都大学, (連合)農学研究科(研究院), 准教授 (30212236)
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Co-Investigator(Kenkyū-buntansha) |
松本 和也 近畿大学, 生物理工学部, 教授 (20298938)
塚本 智史 独立行政法人放射線医学総合研究所, その他部局等, 研究員 (80510693)
|
Project Period (FY) |
2011-04-01 – 2015-03-31
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Keywords | Smyd3 / Epigenetics / mouse embryo / development / Oct4 / Cdx2 |
Outline of Annual Research Achievements |
Smyd3 is a histone H3 lysine 4 (H3K4) di- and tri-methyltransferase that forms a transcriptional complex with RNA polymerase II and activates the transcription of oncogenes and cell cycle genes in human cancer cells. However, the study of Smyd3 in mammalian early embryonic development has not yet been addressed. In the present study, we investigated the expression pattern of Smyd3 in mouse preimplantation embryos and the effects of RNA interference (RNAi)-mediated Smyd3 repression on the development of mouse embryos. Here, we showed that Smyd3 mRNA levels increased after the 2-cell stage, peaked at the 4-cell stage, and gradually decreased thereafter. Moreover, in 2-cell to 8-cell embryos, SMYD3 staining was more intense in the nuclei than in the cytoplasm. In Smyd3-knockdown embryos, the percentage of inner cell mass (ICM)-derived colony formation and trophectoderm (TE)-derived cell attachment was significantly decreased, resulting in a reduction in the number of viable offspring. Furthermore, the expression of Oct4 and Cdx2 during mid-preimplantation gene activation was significantly decreased in Smyd3-knockdown embryos. In addition, the transcription levels of ICM and epiblast markers, such as Oct4, Nanog, and Sox2; of primitive endoderm markers, such as Gata6; and of TE markers, such as Cdx2 and Eomes, were significantly decreased in Smyd3-knockdown blastocysts. These findings indicated that SMYD3 plays an important role in early embryonic lineage commitment and peri-implantation development through the activation of lineage-specific genes.
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Research Progress Status |
26年度が最終年度であるため、記入しない。
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Strategy for Future Research Activity |
26年度が最終年度であるため、記入しない。
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Research Products
(10 results)