2011 Fiscal Year Final Research Report
Epigenetic Regulation in Development and Differentiation
| Project/Area Number |
21249016
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General medical chemistry
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| Research Institution | Osaka University |
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Principal Investigator |
NAKANO Toru 大阪大学, 生命機能研究科, 教授 (00172370)
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| Project Period (FY) |
2009 – 2011
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| Keywords | DNAメチル化 / ヒストン修飾 / エピジェネティクス / クロマチン / 遺伝子発現 / 悪性腫瘍 |
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| Research Abstract |
Establishment of epigenetic state is critically important for development and differentiation of multicellular organisms. In this project, we carried out following three issues on the establishment of epigenetic status.
1. Function of PGC7/ Stella, a regulator of DNA methylation in early embryos.: PGC7/ Stella has the effect to prevent" active DNA demethylation" in early embryos. We identified that the binding of PGC/ Stella to H3K9me2(dimethylated lysine 9 of histone H3) is critically important for the function. During the course of this project, Tet protein plays critical roles in active DNA demethylation by converting 5-methyl cytosine to 5-hydroxymethyl cytosine. Based on this data, we revealed that the binding of Tet-3, the most abundant Tet protein in early embryos, to chromatin is inhibited by PGC7.
2. We analyzed the function of GATA-1 transcription factor using in vitro hematopoietic differentiation induction system from ES cells. Controlled expression of GATA-1 at different time points showed that the function of the factor is quite varied dependent on the time point and its different roles were controlled by epigenetic mechanisms.
3. We find that GS cells(Germline stem cells) are a quite useful resource for studying the biogenesis of piRNA and that the initial phase of piRNA production is carried out in the cells. Using GS cells, we succeeded to identify a protein involved in piRNA biogenesis. In addition, we established a novel experimental system to induce piRNA and subsequent DNA methylation in the transgenic mice.
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[Journal Article] RNAi-mediated knockdown of Xist can rescue the impaired postimplantation development of cloned mouse embryos.2011
Author(s)
Matoba S, Inoue K, Kohda T, Sugimoto M, Mizutani E, Ogonuki N, Nakamura T, Abe K, Nakano T, Ishino F, Ogura A
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Journal Title
Proc Natl Acad Sci USA
Volume: 108
Pages: 20621-6
Peer Reviewed
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[Journal Article] Locus-and domain-dependent control of DNA methylation at mouse B1 retrotransposons during male germ cell development2011
Author(s)
Ichiyanagi K, Li Y, Watanabe T, Ichiyanagi T, Fukuda K, Kitayama J, Yamamoto Y, Kuramochi-Miyagawa S, NakanoT, Yabuta Y, Seki Y, Saitou M, Sasaki H
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Journal Title
Genome Res
Volume: 21
Pages: 2058-66
Peer Reviewed
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[Journal Article] Tudor domain containing 7(Tdrd7) is essential for dynamic ribonucleoprotein(RNP) remodeling of chromatoid bodies during spermatogenesis2011
Author(s)
Tanaka T, Hosokawa M, Vagin VV, ReuterM, Hayashi E, Mochizuki AL, Kitamura K, Yamanaka H, Kondoh G, Okawa K, Kuramochi-Miyagawa S, Nakano T, Sachidanandam R, Hannon GJ, Pillai RS, Nakatsuji N, Chuma S
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Journal Title
Proc Natl Acad Sci USA
Volume: 108
Pages: 10579-10584
Peer Reviewed
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[Journal Article] Regulation of the MDM2-P53 pathway and tumor growth by PICT1 via nucleolar RPL112011
Author(s)
Sasaki M, Kawahara K, Nishio M, MimoriK, Kogo R, Hamada K, Itoh B, Wang J, KomatsuY, Yang YR, Hikasa H, Horie Y, YamashitaT, Kamijo T, Zhang Y, Zhu Y, Prives C, Nakano T, Mak TW, Sasaki T, Maehama T, MoriM, Suzuki A
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Journal Title
Nat Med
Volume: 17
Pages: 944-951
Peer Reviewed
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[Journal Article] Role for piRNAs and a novel non-coding RNA in de novo DNA methylation of the imprinted mouse Rasgrf1 locus2011
Author(s)
Watanabe T, Tomizawa S, Mitsuya K, Totoki Y, Yamamoto Y, Kuramochi-Miyagawa S, Iida N, Hoki Y, Murphy PJ, Toyoda A, Gotoh K, Hiura H, Arima T, Fujiyama A, Sado T, Shibata T, Nakano T, Lin H, Ichiyanagi K, Soloway PD, Sasaki H
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Journal Title
Science
Volume: 332
Pages: 848-852
Peer Reviewed
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[Journal Article] MitoPLD Is a Mitochondrial Protein Essential for Nuage Formation and piRNA Biogenesis in the Mouse Germline2011
Author(s)
Watanabe T, Chuma S, Yamamoto Y, Kuramochi-Miyagawa S, Totoki Y, Toyoda A, Hoki Y, Fujiyama A, Shibata T, Sado T, Noce T, Nakano T, Nakatsuji N, Lin H, Sasaki H
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Journal Title
Dev Cell
Volume: 20
Pages: 364-375
Peer Reviewed
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[Journal Article] MVH in piRNA processing and gene silencing of retrotransposons2010
Author(s)
Kuramochi-Miyagawa S, Watanabe T, Gotoh K, Takamatasu K, Chuma S, Kojima-Kita K, Shiromoto Y, Asada N, Toyoda A, Fujiyama A, Totoki Y, Shibata T, Kimura T, Nakatsuji N, Noce T, Sasaki H, Nakano T
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Journal Title
Genes Dev
Volume: 24
Pages: 887-892
Peer Reviewed
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[Journal Article] The TDRD9-MIWI2 complex is essential for piRNA-mediated retrotransposon silencing in the mouse male germline2009
Author(s)
Shoji M, Tanaka T, Hosokawa M, Reuter M, Stark A, Kato Y, Kondoh G, Okawa K, Chujo, Suzuki T, Hata K, Martin S, Noce T, Kuramochi-Miyagawa S, Nakano T, Sasaki H, Pillai RS, Nakatsuji N, Chuma S
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Journal Title
Dev Cell
Volume: 17
Pages: 775-787
Peer Reviewed
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[Journal Article] Gtsf1/ Cue110, a gene encoding a protein with two copies of a CHHC Zn-finger motif, is involved in spermatogenesis and retrotransposon suppression in murine testes2009
Author(s)
Yoshimura T, Toyoda S, Kuramochi-Miyagawa S, Miyazaki T, Miyazaki S, Tashiro F, Yamato E, Nakano T, Miyazaki J
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Journal Title
Dev Biol
Volume: 335
Pages: 216-217
Peer Reviewed
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