Mechanisms of epigenomic regulation in gametogenesis and genomic imprinting

2012 Fiscal Year Final Research 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 九州大学, 生体防御医学研究所, 教授 (30183825)
• Co-Investigator(Kenkyū-buntansha): HATA Kenichiro 国立成育医療センター研究所, 周産期病態研究部, 部長 (60360335)
• Project Period (FY): 2008 – 2012
• Keywords: 発生・分化 / 発現制御 / 生殖細胞 / エピゲノム / ゲノム刷込み

Research Abstract

In mammalian germ cell development, many epigenetic events including genomic imprinting occur. The changes in the epigenome affect the progression of meiosis and, after fertilization, the developmental potential of the embryo. In this study, we discovered the existence of endogenous siRNA in mouse oocytes, which regulated expression of transposons and genes. We also found that the biogenesis of piRNA in male germ cells requires a phospholipase/nuclease family protein called MitoPLD, and that piRNA is involved in de novo DNA methylation of transposons and a certain imprinted gene(s). Based on the results, we proposed a model in which piRNA-mediated DNA methylation involves nascent noncoding RNA complimentary to the piRNA. Lastly, we developed a method to visualize the DNA methylation status in individual cells.

Research Products

• [Journal Article] Mouse oocyte methylomes at base resolution reveal genome-wide accumulation of non-CpG methylation and role of DNA methyltransferases (2013)
  • Author(s): Shirane, K., Toh, H., Kobayashi, H., Miura, F., Chiba, H., Ito, T., Kono, T. & Sasaki, H
  • Journal Title: PLoS Genet Volume: 9 Pages: e1003439
  • DOI: doi:10.1371/journal.pgen.1003439
  • Peer Reviewed
• [Journal Article] Targeted gene silencing in mouse germ cells by insertion of a homologous DNA into a piRNA generating locus (2013)
  • Author(s): Yamamoto, Y., Watanabe, T., Hoki, Y., Shirane, K., Li, Y., Ichiyanagi, K., Kuramochi-Miyagawa, S., Toyoda, A., Fujiyama, A., Oginuma, M., Suzuki, H., Sado, T., Nakano, T. & Sasaki, H
  • Journal Title: Genome Res Volume: 23 Pages: 292-299
  • DOI: doi:10.1101/gr.137224.112
  • Peer Reviewed
• [Journal Article] Accumulation and loss of asymmetric non-CpG methylation during male germ-cell development. Nucl (2013)
  • Author(s): Ichiyanagi, T., Ichiyanagi, K., Miyake, M. & Sasaki, H
  • Journal Title: Acids Res Volume: 41 Pages: 738-745
  • DOI: doi:10.1093/nar/gks1117
  • Peer Reviewed
• [Journal Article] An atomic model of ZFP57 recognition of CpG methylation within a specific DNA sequence (2012)
  • Author(s): Liu, Y., Toh, H., Sasaki, H., Zhang, X. & Cheng, X
  • Journal Title: Genes Dev Volume: 26 Pages: 2374-2379
  • DOI: doi:10.1101/gad.202200.112
  • Peer Reviewed
• [Journal Article] Sequences in the H19 ICR that are transcribed as small RNA in oocytes are dispensable for methylation imprinting in YAC transgenic mice (2012)
  • Author(s): Takahashi, T., Matsuzaki, H., Tomizawa, S., Okamura, E., Ichiyanagi, T., Fukamizu, A., Sasaki, H. & Tanimoto, K
  • Journal Title: Gene Volume: 508 Pages: 26-34
  • DOI: doi:10.1016/j.gene.2012.07.062
  • Peer Reviewed
• [Journal Article] Genomic imprinting and its relevance to congenital disease, infertility, molar pregnancy and induced pluripotent stem cells (2012)
  • Author(s): Tomizawa, S. & Sasaki, H
  • Journal Title: J. Hum. Genet Volume: 57 Pages: 84-91
  • DOI: doi:10.1038/jhg.2011.151
  • Peer Reviewed
• [Journal Article] Active role of small non-coding RNAs derived from SINE/B1 retrotransposon during early mouse development (2012)
  • Author(s): Ohnishi, Y., Totoki, Y., Toyoda, A., Watanabe, T., Yamamoto, Y., Tokunaga, K., Sakaki, Y., Sasaki, H. & Hohjoh, H
  • Journal Title: Mol. Biol. Rep Volume: 39 Pages: 903-909
  • DOI: doi:10.1007/s11033-011-0815-1
  • Peer Reviewed
• [Journal Article] Re-investigation and RNA sequencing-based identification of genes with placenta-specific imprinted expression (2012)
  • Author(s): Okae, H., Hiura, H., Miyauchi, N., Abe, C., Nishida, Y., Funayama, R., Tanaka, S., Chiba, H., Yaegashi, N., Nakayama, K., Sasaki, H. & Arima, T
  • Journal Title: Hum. Mol. Genet Volume: 21 Pages: 548-558
  • DOI: doi:10.1093/hmg/ddr488
  • Peer Reviewed
• [Journal Article] Locus- and domain-dependent control of DNA methylation at mouse B1 retrotransposons during male germ cell development (2011)
  • Author(s): Ichiyanagi, T., Fukuda, K., Kitayama, J., Yamamoto, Y., Kuramochi-Miyagawa, S., Nakano, T., Yabuta, Y., Seki, Y., Saitou, M., & Sasaki, H
  • Journal Title: Genome Res Volume: 21 Pages: 2058-2066
  • DOI: doi:10.1101/gr.123679.111
  • Peer Reviewed
• [Journal Article] Role for piRNAs and non-coding RNA in de novo DNA methylation of the imprinted mouse Rasgrf1 locus (2011)
  • Author(s): Watanabe, T., Tomizawa, S., Mitsuya, K., Totoki, Y., Yamamoto, Y., Kuramochi-Miyagawa, S., Iida, N., Hoki, Y., Murphy, P.J., Toyoda, A., Gotoh, K., Hiura, H., Arima, T., Fujiyama, A., Sado, T., Shibata, T., Nakano, T., Lin, H., Ichiyanagi, K., Soloway, P.D. & Sasaki, H
  • Journal Title: Science Volume: 332 Pages: 848-52
  • DOI: doi:10.1126/science.1203919
  • Peer Reviewed
• [Journal Article] Genomic imprinting in mammals: its life cycle, molecular mechanisms and reprogramming (2011)
  • Author(s): Li, Y. & Sasaki, H
  • Journal Title: Cell Res Volume: 21 Pages: 466-473
  • DOI: doi:10.1038/cr.2011.15
  • Peer Reviewed
• [Journal Article] MitoPLD is a mitochondrial protein essential for nuage formation and piRNA biogenesis in the mouse germline (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 Volume: 20 Pages: 364-375
  • DOI: doi:10.1016/j.devcel.2011.01.005
  • Peer Reviewed
• [Journal Article] Dynamic stage-specific changes of imprinted differentially methylated regions during early mammalian development and prevalence of non-CpG methylation in oocytes (2011)
  • Author(s): Tomizawa, S., Kobayashi, H., Watanabe, T., Andrews, S., Hata, K., Kelsey, G. & Sasaki, H
  • Journal Title: Development Volume: 138 Pages: 811-820
  • DOI: doi:10.1242/dev.061416
  • 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 Volume: 42 Pages: 1093-1100
  • DOI: doi:10.1038/ng.708
  • Peer Reviewed
• [Journal Article] Small RNA class transition from siRNA/piRNA to miRNA during pre-implantation mouse development. Nucl (2010)
  • Author(s): Ohnishi, Y., Totoki, Y., Toyoda, A., Watanabe, T., Yamamoto, Y., Tokunaga, K., Sakaki, Y., Sasaki, H. & Hohjoh, H
  • Journal Title: Acids Res Volume: 38 Pages: 5141-5151
  • DOI: doi:10.1093/nar/gkq229
  • Peer Reviewed
• [Journal Article] region within the Gpr1-Zdbf2 imprinted domain on mouse chromosome 1 identified by meDIP-on-chip (2010)
  • Author(s): Hiura, H., Sugawara, A., Ogawa, H., John, R., Miyauchi, N., Miyanari, Y., Horiike, T., Li, Y., Yaegashi, N., Sasaki, H., Kono, T. & Arima, T
  • Journal Title: Nucl. Acids Res Volume: 38 Pages: 4929-4945
  • DOI: doi:10.1093/nar/gkq200
  • 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 Volume: 24 Pages: 887-892
  • DOI: doi:10.1101/gad.1902110
  • Peer Reviewed
• [Journal Article] Genetic evidence for Dnmt3a-dependent imprinting during oocyte growth obtained by conditional knockout with Zp3-Cre and complete exclusion of Dnmt3b by chimera formation (2010)
  • Author(s): Kaneda, M., Hirawasa, R., Chiba, H., Okano, M., Li, E. & Sasaki, H
  • Journal Title: Genes Cells Volume: 15 Pages: 169-179
  • DOI: doi:10.1111/j.1365-2443.2009.01374
  • Peer Reviewed
• [Journal Article] The TDRD9-MIWI2 complex is essential for piRNA-mediated retrotransposon silencing in the mouse male 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, S.L., Noce, T., Kuramochi-Miyagawa, S., Nakano, T., Sasaki, H., Pillai, R.S., Nakatsuji, N. & Chuma, S
  • Journal Title: Dev. Cell Volume: 17 Pages: 775-787
  • DOI: doi:10.1016/j.devcel.2009
  • Peer Reviewed
• [Journal Article] Conditional knockdown of Nanog induces apoptotic cell death in mouse migrating primordial germ cells (2009)
  • Author(s): Yamaguchi, S., Kurimoto, K., Yabuta, Y., Sasaki, H., Nakatsuji, N., Saitou, M. & Tada, T
  • Journal Title: Development Volume: 136 Pages: 4011-4020
  • DOI: doi:10.1242/dev.041160
  • Peer Reviewed
• [Journal Article] Abnormal DNA methyltransferase expression in mouse germline stem cells results in spermatogenesis defects (2009)
  • Author(s): Takashima, S., Takehashi, M., Lee, J., Chuma, S. Okano, M., Hata, K. Suetake, I., Nakatsuji, N., Miyoshi, H., Tajima, S., Tanaka, Y., Toyokuni, S., Sasaki, H., Kanatsu-Shinohara, M. & Shinohara, T
  • Journal Title: Biol. Reprod Volume: 81 Pages: 155-164
  • DOI: doi:10.1095/biolreprod.108.074708
  • Peer Reviewed
• [Journal Article] Identification of the mouse paternally expressed imprinted gene Zdbf2 on chromosome 1 and its imprinted human homolog ZDBF2 on chromosome 2 (2009)
  • Author(s): Kobayashi, H., Yamada, K., Morita, S., Hiura, H., Fukuda, A., Kagami, M., Ogata, T., Hata, K., Sotomaru, Y. & Kono, T
  • Journal Title: Genomics Volume: 93 Pages: 461-72
  • DOI: doi:10.1016/j.ygeno.2008.12.012
  • Peer Reviewed
• [Journal Article] Histone methylation is mechanistically linked to DNA methylation at imprinting control regions in mammals (2009)
  • Author(s): Henckel, A., Nakabayashi, K., Sanz, LA., Feil, R., Hata, K. & Arnaud, P
  • Journal Title: Hum Mol Genet Volume: 18 Pages: 3375-83
  • DOI: doi:10.1093/hmg/ddp277
  • Peer Reviewed
• [Journal Article] Dynamic transition of Dnmt3b expression in mouse pre- and early post-implantation embryos (2009)
  • Author(s): Hirasawa, R. & Sasaki, H
  • Journal Title: Gene Expr. Patt Volume: 9 Pages: 27-30
  • DOI: doi:10.1016/j.gep.2008.09.002
  • Peer Reviewed
• [Journal Article] De novo DNA methylation independent establishment of maternal imprint on X chromosome in mouse oocytes (2008)
  • Author(s): Chiba, H., Hirasawa, R., Kaneda, M., Amakawa, Y., Li, E., Sado, T. & Sasaki, H
  • Journal Title: Genesis Volume: 46 Pages: 768-774
  • DOI: doi:10.1002/dvg.20496
  • Peer Reviewed
• [Journal Article] Maternal and zygotic Dnmt1 are necessary and 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 Volume: 22 Pages: 1607-1616
  • DOI: doi:10.1101/gad.1667008
  • Peer Reviewed
• [Journal Article] Endogenous siRNAs from naturally formed dsRNAs 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, M.A., Sakaki, Y. & Sasaki, H
  • Journal Title: Nature Volume: 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 Volume: 22 Pages: 908-917
  • DOI: doi:10.1101/gad.1640708
  • Peer Reviewed
• [Presentation] Mammalian germline small RNAs and epigenetic programming. Gordon Research Conference (Epigenetics) (2011)
  • Author(s): Sasaki, H
  • Organizer: Easton
  • Place of Presentation: MA, USA
  • Year and Date: 2011-08-09
• [Presentation] Imprinting, DNA methylation and small RNA in germ cells (2009)
  • Author(s): Sasaki, H
  • Organizer: Cold Spring Harbor Laboratory/Wellcome Trust Joint Conference "Mouse Genetics & Genomics: Development & Disease"
  • Place of Presentation: Hinxton, UK
  • Year and Date: 20090903-06
• [Presentation] Genomic imprinting, DNA methylation and small RNAs in mammalian germ cells (2009)
  • Author(s): Sasaki, H.
  • Organizer: Gordon Research Conference "Epigenetics- The Role of the Environment and Epigenetic Mechanisms in Bahavior, Health, and Disease", Holderness
  • Place of Presentation: NH, USA
  • Year and Date: 20090809-14
• [Book] 卵子学 (2011)
  • Author(s): 佐々木裕之
  • Total Pages: 103-109
  • Publisher: 京都大学学術出版会
• [Book] 4章.ゲノムの高度活用戦術-エピジェネティクス.現代生物科学入門1ゲノム科学の基礎 (2009)
  • Author(s): 佐々木裕之
  • Total Pages: 153-200
  • Publisher: 岩波書店
• [Book] Genomic imprinting and X chromosome inactivation in germ cell development. Genetic and Epinenetic Control of Mammalian Germ Cell Development and Function (ed. Nozaki, M) (2009)
  • Author(s): Kaneda, M. & Sasaki, H.
  • Total Pages: 37-56
  • Publisher: Research Signopost
• [Remarks]
  • URL: http://www.bioreg.kyushu-u.ac.jp/labo/epigenome/index.html