Analysis of genome inactivation mechanism using chromosomal site-specific gene integration

• Project/Area Number: 23651189
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Genome biology
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: ABE KUNIYA 独立行政法人理化学研究所, バイオリソースセンター, チームリーダー (40240915)
• Co-Investigator(Renkei-kenkyūsha): ARAKI Araki 熊本大学, 生命資源研究・支援センター, 准教授 (90211705)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: X染色体不活性化 / 偽常染色体 / エピジェネティクス / 遺伝子導入技術 / エピジェネティックス / ヒストン修飾 / 遺伝子導入 / 遺伝子トラップ

Research Abstract

In this study, we first devised a site-specific gene integration method, and established two female mouse lines, whose two X chromosomes carry different fluorescent protein genes. X chromosome inactivation phenomenon can be visualized using these mouse lines. Processes of X inactivation and reactivation can be analyzed in living cells of these mouse lines for the first time.
Using female somatic cells isolated from hybrid individuals between Xist knockout mice and asian mouse subspecies, ChIP-Seq analysis of histone modifications has been conducted. Differences in epigenetic states between inactive X and active X has been revealed.

Research Products

• [Journal Article] Understanding the X chromosome inactivation cycle in mice: A comprehensive view provided by nuclear transfer. (2014)
  • Author(s): Oikawa M, Inoue K, Shiura H, Matoba S, Kamimura S, Hirose M, Mekada K, Yoshiki A, Tanaka A, Abe K, Ishino F, Ogura A.
  • Journal Title: Epigenetics Volume: 9 Issue: 2 Pages: 204-211
  • DOI: 10.4161/epi.26939
  • Peer Reviewed / Open Access
• [Journal Article] Genome-wide analysis of the chromatin composition of histone H2A and H3 variants in mouse embryonic stem cells. (2014)
  • Author(s): Yukawa, M. et al.
  • Journal Title: PLOS One Volume: 9 Issue: 3 Pages: e92689-e92689
  • DOI: 10.1371/journal.pone.0092689
  • Peer Reviewed / Open Access
• [Journal Article] Generation of a novel germline stem cell line expressing a germline-specific reporter in the mouse. (2013)
  • Author(s): Shiura H, Ikeda R, Lee J, Sato T, Ogonuki N, Hirose M, Ogura A, Ogawa T, Abe K.
  • Journal Title: Genesis Volume: Epub ahead of print Issue: 7 Pages: 498-505
  • DOI: 10.1002/dvg.22391
  • Peer Reviewed
• [Journal Article] RNAi-mediated knockdown of Xist does not rescue the impaired development of female cloned mouse embryos (2013)
  • Author(s): Oikawa M, Matoba S, Inoue K, Kamimura S, Hirose M, Ogonuki N, Shiura H, Sugimoto M, Abe K, Ishino F, and Ogura A
  • Journal Title: J. Repord. Dev Volume: 59 Pages: 231-237
  • NAID: 10031184751
  • Peer Reviewed
• [Journal Article] Max is a repressor of germ-cell-related gene expression in mouse embryonic stem cells (2013)
  • Author(s): Maeda, I., Okamura, D., Tokitake, Y., Ikeda, M, Kawaguchi, H., Mise, N., Abe, K., Noce, T., Okuda, A, Matsui, Y
  • Journal Title: Nature Communications Volume: 4 Issue: 1 Pages: 1754-1754
  • DOI: 10.1038/ncomms2780
  • Peer Reviewed
• [Journal Article] Large, male germ cell-specific hypomethylated DNA domains with unique genomic and epigenomic features on the mouse X chromosome. (2013)
  • Author(s): Ikeda, R. et al.
  • Journal Title: DNA Res. Volume: 20 Issue: 6 Pages: 549-565
  • DOI: 10.1093/dnares/dst030
  • Peer Reviewed
• [Journal Article] The REV7 subunit of DNA polymerase ζ is essential for primordial germ cell maintenance in the mouse. (2013)
  • Author(s): Watanabe, N., Mii, S., Asai, N., Asai, M., Niimi, K., Ushida, K., Kato, T., Enomoto, A., Ishii, H., Takahashi, M., Murakumo, Y.
  • Journal Title: J. Biol. Chem. Volume: 288 Issue: 15 Pages: 10459-10471
  • DOI: 10.1074/jbc.m112.421966
  • Peer Reviewed
• [Journal Article] Epigenetic regulation of sex determination by the histone demethylase Jmjd1a (2013)
  • Author(s): Kuroki S, Matoba S, Akiyoshi M, Matsumura Y, Miyachi H, Mise N, Abe K, Ogura A, Wilhelm D, Koopman P, Nozaki M, Kanai Y, Shinkai Y, and Tachibana, M
  • Journal Title: Science Volume: 341 Issue: 6150 Pages: 1106-1109
  • DOI: 10.1126/science.1239864
  • Peer Reviewed
• [Journal Article] RNAi-mediated Knockdown of <i>Xist</i> Does Not Rescue the Impaired Development of Female Cloned Mouse Embryos (2013)
  • Author(s): Oikawa, et al.
  • Journal Title: Journal of Reproduction and Development Volume: 59 Issue: 3 Pages: 231-237
  • DOI: 10.1262/jrd.2012-195
  • NAID: 10031184751
  • ISSN: 0916-8818, 1348-4400
  • Peer Reviewed
• [Journal Article] Cell-cycle gene-specific control of transcription has a critical role in proliferation of primordial germ cells (2012)
  • Author(s): Okamura, D., Maeda, I., Taniguchi, H., Tokitake, Y., Ikeda, M., Ozato, K., Mise, N., Abe, K., Noce, T., Izpisua Belmonte, J. C. and Matsui, Y
  • Journal Title: Genes & Development Volume: 26 Issue: 22 Pages: 2477-2482
  • DOI: 10.1101/gad.202242.112
  • Peer Reviewed
• [Journal Article] Molecular identification of t^<w5>: Vps52 promotes pluripotential cell differentiation through cell-cell interactions. (2012)
  • Author(s): Sugimoto, M., Kondo, M., Hirose, M., Suzuki, M., Mekada, K., Abe, T., Kiyonari, H., Ogura, A., Takagi, N., Artzt, K. and Abe, K.
  • Journal Title: Cell Reports Volume: Vol.2 Issue: 5 Pages: 1363-1374
  • DOI: 10.1016/j.celrep.2012.10.004
  • Peer Reviewed
• [Journal Article] Ectopic expression of Ptf1a induces spinal defects, urogenital defects and anorectal malformations in Danforth's short tail mice. (2012)
  • Author(s): Semba, K., Araki, K., Matsumoto, K.-I., Suda, H., Ando, T. Sei, A., Mizuta, H., Takagi, K., Nakahara, M., Muta, M., Yamada, G., Nakagata, N., Iida, A., Ikegawa, Y., Araki, M., Abe, K. and Yamamura, K.
  • Journal Title: PLoS Genet. Volume: Vol.9 Issue: 2 Pages: 1-17
  • DOI: 10.1371/journal.pgen.1003204
  • Peer Reviewed
• [Journal Article] High resolution intravital imaging of subcellular structures of mouse abdominal organs using a microstage device. (2012)
  • Author(s): Cao, L, Kobayakawa, S., Yoshiki, A., Abe, K.
  • Journal Title: PLoS One Volume: 7 Issue: 3 Pages: e33876-e33876
  • DOI: 10.1371/journal.pone.0033876
  • Peer Reviewed
• [Journal Article] Highly parallel SNP genotyping reveals high-resolution landscape of mono-allelic Ube3a expression associated with locus-wide antisense transcription (2011)
  • Author(s): Numata K., et al
  • Journal Title: Nucleic Acids Res. Volume: 39 Issue: 7 Pages: 2649-2657
  • DOI: 10.1093/nar/gkq1201
  • Peer Reviewed
• [Journal Article] Incomplete X-inactivation initiated by a hypomorphic Xist allele in the mouse (2011)
  • Author(s): Hoki, Y., et al
  • Journal Title: Development Volume: 138 Issue: 13 Pages: 2649-2659
  • DOI: 10.1242/dev.061226
  • Peer Reviewed
• [Journal Article] RNAi-mediated knockdown of Xist can rescue the impaired postimplantation development of cloned mouse embryos (2011)
  • Author(s): Matoba S, et al
  • Journal Title: Proc Natl Acad Sci USA Volume: 108 Issue: 51 Pages: 20621-20626
  • DOI: 10.1073/pnas.1112664108
  • Peer Reviewed
• [Presentation] マウス着床期における Xist/Tsix ダイナミクス (2013)
  • Author(s): 志浦寛相, 阿部訓也
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 神戸
  • Year and Date: 2013-12-03
• [Presentation] マウス多能性胚細胞・生殖細胞発生プログラムの包括的解析 (2013)
  • Author(s): 阿部訓也
  • Organizer: 第9回環境エピゲノミクス研究会
  • Place of Presentation: 東京
  • Year and Date: 2013-06-15
• [Presentation] マウス生殖細胞で発現するX連鎖遺伝子群に見出された特徴的なエピジェネティック修飾 (2012)
  • Author(s): 池田理恵子, 志浦寛相, 沼田興治, 細川美穂子, 近藤昌代, 中馬新一郎, 阿部訓也
  • Organizer: 日本遺伝学会第84回大会
  • Place of Presentation: 福岡
  • Year and Date: 2012-09-25
• [Presentation] tw5変異マウスの解析で明らかになったVps52遺伝子の多能性幹細胞分化制御因子としての役割 (2012)
  • Author(s): 杉本道彦、近藤昌代、阿部訓也
  • Organizer: 日本遺伝学会第84回大会
  • Place of Presentation: 福岡
• [Presentation] マウス生殖幹細胞のゲノム-エピゲノム解析 (2012)
  • Author(s): 細川美穂子、刀谷在美、林瑛理、望月綾子、末盛博文、沼田興治、阿部訓也、田中敬、篠原美都、篠原隆司、中辻憲夫、中馬新一郎
  • Organizer: 日本遺伝学会第84回大会
  • Place of Presentation: 福岡
• [Presentation] Dynamics of epigenomic changes during development of early embryos and primordial germ cells in mice. (2011)
  • Author(s): Kuniya Abe, Koji Numata, Rieko Ikeda, Hirosuke Shiura and Michihiko Sugimoto
  • Organizer: 50 Years of X Inactivation Research - 3rd X-inactivation meeting
  • Place of Presentation: Oxford (イギリス)
• [Presentation] Region-wide DNA methylation and gene expression of the X-linked genes in mouse germ line. (2011)
  • Author(s): Rieko Ikeda, Hirosuke Shiura, Nathan Mise, Masayo Kondo, Kuniya Abe
  • Organizer: 50 Years of X Inactivation Research - 3rd X-inactivation meeting
  • Place of Presentation: Oxford (イギリス)
• [Book] 「新しいリサーチツールとしてのバイオイメージング(蛍光イメージングを中心に)」「 series モデル動物利用マニュアル 生物機能モデルと新しいリソース・リサーチツール」 (2011)
  • Author(s): 阿部訓也
  • Publisher: 株式会社エル・アイ・シー
• [Book] 『series モデル動物利用マニュアル 生物機能モデルと新しいリソース・リサーチツール』 (2011)
  • Author(s): 阿部訓也
  • Total Pages: 671
  • Publisher: 株式会社 エル・アイ・シー
• [Remarks]
  • URL: http://www.brc.riken.jp/lab/mcd/mcd/