Epigenomic mechanisms in gametogenesis and genomic imprinting

2010 Fiscal Year Self-evaluation Report

• Project Area: The germline: its developmental cycle and epigenome network
• Project/Area Number: 20062010
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Kyushu University (2010-2012); National Institute of Genetics (2008-2009)
• Principal Investigator: SASAKI Hiroyuki National Institute of Genetics, 生体防御医学研究所, 教授 (30183825)
• Project Period (FY): 2008 – 2012
• Keywords: 発生・分化 / 発現制御 / 生殖細胞 / エピゲノム / ゲノム刷り込み

Research Abstract

哺乳類の生殖細胞の発生・分化過程で生じるゲノム刷込み等の多様なエピゲノム修飾の変化を制御するネットワークを明らかにする。具体的には、(1)DNAメチル化酵素やその他のエピジェネティック修飾酵素と相互作用し、その標的特異性等に関わる因子を同定する、(2)生殖細胞のsiRNAやpiRNAの生成機構、生理的な意義、それらがメチル化を誘導する経路を明らかにする、(3)個々の細胞で特定の配列のDNAメチル化状態を可視化する技術を開発し、生殖細胞や初期胚の研究に応用することを目指して研究を行う。修飾酵素がどのようにして特異的な標的を認識するのかはエピジェネティクスの重要な課題であり、以上を以て、不妊や習慣流産の解明、生殖医療、クローン作成技術の向上などへの貢献をめざす。

Research Products

• [Journal Article] MitoPLD is a mitochondrialprotein essential for nuage formationand piRNA biogenesis in the mousegermline (2011)
  • 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.
  • Journal Title: Dev Cell 20 Pages: 364-375
  • Peer Reviewed
• [Journal Article] Dynamic stage-specific changes of imprinted differentially methylated regions during early mammalian development and prevalence of non-CpGmethylation in oocytes. (2011)
  • Author(s): Tomizawa, S, Kobayashi, H, Watanabe, T, Andrews, S, Hata, K, Kelsey, G, Sasaki, H.
  • Journal Title: Development 138 Pages: 811-829
  • Peer Reviewed
• [Journal Article] Targets and dynamics of promoter DNA methylation during early mouse development. (2010)
  • Author(s): Borgel, J, Guibert, S, Li, Y, Chiba, H, Schuebeler, D, Sasaki, H, Forne, T, Weber, M.
  • Journal Title: Nat Genet 42 Pages: 1093-1100
  • Peer Reviewed
• [Journal Article] MVH in piRNA processing and gene silencing of retrotransposons (2010)
  • Author(s): Kuramochi-Miyagawa, S, Watanabe, T, Gotoh, K, Takamatsu, K, Chuma, S, Kojima-Kita, K, Shiromoto, Y, Asada, N, Kimura, T, Nakatsuji, N, Noce, T, Sasaki, H, Nakano, T.
  • Journal Title: Genes Dev 24 Pages: 887-892
  • Peer Reviewed
• [Journal Article] The TDRD9-MIWI2 complex is essential for piRNA-mediated retrotransposon silencing in the mousemale germline (2009)
  • Author(s): Shoji, M, Tanaka, T, Hosokawa, M, Reuter, M, Stark, A, Kato, Y, Kondoh, G, Okawa, K, Chujo, T, Suzuki, T, Hata, K, Martin, SL, Noce, T, Kuramochi-Miyagawa, S, Nakano, T, Sasaki, H, Pillai, RS, Nakatsuji, N, Chuma, S.
  • Journal Title: Dev Cell 17 Pages: 775-787
  • Peer Reviewed
• [Journal Article] Maternal and zygotic Dnmt1 are necessaryand sufficient for the maintenance of DNA methylation imprints during preimplantation development. (2008)
  • Author(s): Hirasawa, R, Chiba, H, Kaneda, M, Tajima, S, Li, E, Jaenisch, R, Sasaki, H.
  • Journal Title: Genes Dev 22 Pages: 1607-1616
  • Peer Reviewed
• [Journal Article] Endogenous siRNAs from naturally for medds RNAs regulate transcripts in mouse oocytes. (2008)
  • Author(s): Watanabe, T, Totoki, Y, Toyoda, A, Kaneda, M, Kuramochi-Miyagawa, S, Obata, Y, Chiba, H, Kohara, Y, Kono, T, Nakano, T, Surani, MA, Sakaki, Y, Sasaki, H.
  • Journal Title: Nature 453 Pages: 539-543
  • Peer Reviewed
• [Journal Article] DNA methylation of retrotransposon genes is regulated by Piwi family members MILI and MIWI2 in murine fetal testes. (2008)
  • Author(s): Kuramochi-Miyagawa, S, Watanabe, T, Gotoh, K, Totoki, Y, Toyoda, A, Ikawa, M, Asada, N, Kojima, K, Yamaguchi, Y, Ijiri, T, Hata, K, Li, E, Matsuda, Y, Kimura, T, Okabe, M, Sakaki, Y, Sasaki, H, Nakano, T.
  • Journal Title: Genes Dev 22 Pages: 908-917
  • Peer Reviewed
• [Journal Article] Role for piRNAs and non-coding RNA in de novo DNA methylation of the imprinted mouse Rasgrf1 locus.
  • 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.
  • Journal Title: Science in press
  • Peer Reviewed
• [Presentation] Role for Piwi-interacting RNA and a novel noncoding RNA in de novo DNA methylation of the imprinted mouse Rasgrf1 locus in the germline. (2010)
  • Author(s): Sasaki, H., Watanabe, T.
  • Organizer: Cold Spring Harbor Asia Meeting on Epigenetics, Chromatin & Transcription.
  • Place of Presentation: Suzhou, China.
  • Year and Date: 20100417-20100421
• [Presentation] Genomic imprinting, DNA methylation and small RNAs in mammaliangerm cells. (2009)
  • Author(s): Sasaki, H.
  • Organizer: Gordon Research Conferenceon Epigenetics-The Role of the Environment and Epigenetic Mechanisms
  • Place of Presentation: Holderness, NH, USA.
  • Year and Date: 20090809-20090814
• [Presentation] The epigenome and small RNA repertoire in mammalian germ cells. (2009)
  • Author(s): Sasaki, H.
  • Organizer: EMBO Conference Series on Chromatin and Epigenetics
  • Place of Presentation: Heidelberg, Germany.
  • Year and Date: 20090513-20090517
• [Book] 現代生物科学入門-1ゲノム科学の基礎(浅島誠, 黒岩常祥, 小原雄治編)(4章ゲノムの高度活用戦略-エピジェネティクス) (2009)
  • Author(s): 佐々木裕之
  • Total Pages: 153-200
  • Publisher: 岩波書店