ESTABLISHMENT OF EPIGENOMIC ANALYSIS TECHNOLOGY AND ITS APPLICATION TO MEDICAL GENETICS

• Project/Area Number: 19209011
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Human genetics
• Research Institution: National Institute of Genetics
• Principal Investigator: SASAKI Hiroyuki National Institute of Genetics, 総合遺伝研究系, 教授 (30183825)
• Co-Investigator(Kenkyū-buntansha): NAKAO Mitsuyoshi 熊本大学, 発生医学研究所, 教授 (00217663)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥48,490,000 (Direct Cost: ¥37,300,000、Indirect Cost: ¥11,190,000); Fiscal Year 2008: ¥23,140,000 (Direct Cost: ¥17,800,000、Indirect Cost: ¥5,340,000); Fiscal Year 2007: ¥25,350,000 (Direct Cost: ¥19,500,000、Indirect Cost: ¥5,850,000)
• Keywords: エピジェネティクス / エピゲノム / DNAメチル化 / クロマチン / マイクロアレイ / 遺伝学 / 癌 / 発生・分化

Research Abstract

エピゲノムは細胞のエピジェネティックな修飾の総体であり、発生・分化・がん等において重要な働きをする。網羅的・体系的なエピゲノム解析基盤を確立する目的で研究を行い、(1)独自のメチル化DNA濃縮ツールを開発し、(2)マウスの細胞を用いて網羅的解析技術を確立し、(3)この方法をヒト培養細胞や健常者・各種疾患由来の細胞に応用した。これにより、(4)様々なクロマチン因子の相互作用や標的配列を同定することに成功し、(5)ヒト・チンパンジー間のDNAメチル化の差を同定し、エピジェネティクスの制御機構や多様性・進化との関わりを研究する基盤を確立した。

Research Products

• [Journal Article] Abnormal DNA methyltransferase expression in mouse germline stem cells results in spermatogenesis defects (2009)
  • Author(s): S. Takashima, M. Takehashi, J. Lee, S. Chuma, M. Okano, K. Hata, I. Suetake, N. Nakatsuji, H. Miyoshi, S. Tajima, Y. Tanaka, S. Toyokuni, H. Sasaki, M. Kanatsu-Shinohara, and T. Shinohara.
  • Journal Title: Biol. Reprod. (in press)
  • Peer Reviewed
• [Journal Article] Architectural roles of multiple chromatin insulators at the human apolipoprotein gene cluster (2009)
  • Author(s): T. Mishiro, K. Ishihara, S. Hino, S. Tsutsumi, H. Aburatani, K. Shirahige, Y. Kinoshita, and M. Nakao
  • Journal Title: EMBO J. (in press)
  • Peer Reviewed
• [Journal Article] MCAF1/AM is involved in Sp1-mediated maintenance of cancer- associated telomerase activity (2009)
  • Author(s): L. Liu, K. Ishihara, T. Ichimura, N. Fujita, S. Hino, S. Tomita, S. Watanabe, N. Saitoh, T. Ito, and M. Nakao.
  • Journal Title: J. Biol. Chem. 284 Pages: 5165-5174
  • Peer Reviewed
• [Journal Article] HMGA2 maintains oncogenic RAS-induced epithelial- mesenchymal transition in human pancreatic cancer cells (2009)
  • Author(s): S. Watanabe, Y. Ueda, S. Akaboshi, Y. Hino, Y. Sekita, and M. Nakao
  • Journal Title: Am. J. Pathol. 174 Pages: 854-868
  • Peer Reviewed
• [Journal Article] MCAF1/AM is involved in Sp1-mediated maintenance of cancer-associated telomerase activity. (2009)
  • Author(s): Liu, L., et al.
  • Journal Title: J. Biol. Chem. 284 Pages: 5165-5174
  • Peer Reviewed
• [Journal Article] HMGA2 maintains oncogenic RAS-induced epithelial-mesenchymal transition in human pancreatic cancer cells. (2009)
  • Author(s): Watanabe, S., et al.
  • Journal Title: Am. J. Pathol. 174 Pages: 854-868
  • Peer Reviewed
• [Journal Article] Architectural roles of multiple chromatin insulators at the human apolipoprotein gene cluster. (2009)
  • Author(s): Mishiro, T., et al.
  • Journal Title: EMBO J. (In press)
  • Peer Reviewed
• [Journal Article] Abnormal DNA methyltransferase expression in mouse germline stem cells results in spermatogenesis defects. (2009)
  • Author(s): Takashima, S., et al.
  • Journal Title: Biol. Reprod. (In press)
  • Peer Reviewed
• [Journal Article] Epigenetic events in mammalian germ-cell development: reprogramming and beyond (2008)
  • Author(s): H. Sasaki and Y. Matsui
  • Journal Title: Nat. Rev. Genet. 9 Pages: 129-140
  • 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): S. Kuramochi-Miyagawa, T. Watanabe, K. Gotoh, Y. Totoki, A. Toyoda, M. Ikawa, N. Asada, K. Kojima, Y. Yamaguchi, T. Ijiri, K. Hata, E. Li, Y. Matsuda, T. Kimura, M. Okabe, Y. Sakaki, H. Sasaki, and T. Nakano
  • Journal Title: Genes Dev. 22 Pages: 908-917
  • 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): R. Hirasawa, H. Chiba, M. Kaneda, S. Tajima, E. Li, R. Jaenisch, and H. Sasaki
  • Journal Title: Genes Dev. 22 Pages: 1607-1616
  • Peer Reviewed
• [Journal Article] Polycomb group protein-associated chromatin is reproduced in post-mitotic G1 phase and required for S phase progression (2008)
  • Author(s): T. Aoto, N. Saitoh, Y. Sakamoto, S. Watanabe, and M. Nakao
  • Journal Title: J. Biol. Chem. 283 Pages: 18905-18915
  • Peer Reviewed
• [Journal Article] Cohesin mediates transcriptional insulation by CCCTC-binding factor (2008)
  • Author(s): K.S. Wendt, K. Yoshida, T. Itoh, M. Bando, B. Koch, E. Schirghuber, S. Tsutsumi, G. Nagae, K. Ishihara, T. Mishiro, K. Yahata, F. Imamoto, H. Aburatani, M. Nakao, N. Imamoto, K. Maeshima, K. Shirahige, and J.M. Peters
  • Journal Title: Nature 451 Pages: 796-803
  • Peer Reviewed
• [Journal Article] 細胞のエピジェネティクス (2008)
  • Author(s): 富澤信一, 佐々木裕之
  • Journal Title: 遺伝子医学MOOK (別冊 進み続ける細胞移植治療の実際-再生医療の実現に向けた科学・技術と周辺要素の理解) Pages: 145-148
• [Journal Article] エピジェネティクス-疾患を見つめる新たな視点 (2008)
  • Author(s): 古海弘康, 佐々木裕之
  • Journal Title: BIO Clinica 23 Pages: 155-159
• [Journal Article] 遺伝か環境か? (2008)
  • Author(s): 古海弘康, 佐々木裕之
  • Journal Title: エピジェネティクスの視点から. 医学のあゆみ (臨床ゲノム研究-成果と課題) 225 Pages: 949-953
• [Journal Article] ゲノムインプリンティング (2008)
  • Author(s): 平澤竜太郎, 佐々木裕之
  • Journal Title: 生体の科学 (増大特集 現代医学・生物学の仮説・学説2008) 59 Pages: 402-403
• [Journal Article] Polycomb group protein-associated chromatin is reproduced in post-mitotic G1 phase and required for S phase progression. (2008)
  • Author(s): Aoto, T., et al.
  • Journal Title: J. Biol. Chem. 283 Pages: 18905-18915
  • Peer Reviewed
• [Journal Article] Cohesin mediates transcriptional insulation by CCCTC-binding factor. (2008)
  • Author(s): Wendt, K. S., et al.
  • Journal Title: Nature 451 Pages: 796-803
  • 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, et al.
  • Journal Title: Genes Dev. 22 Pages: 908-917
  • Peer Reviewed
• [Journal Article] Maternal and zygotic Dnmtl are necessary and sufficient for thc maintenance of DNA methylation imprints during preimplantation development. (2008)
  • Author(s): Hirasawa, R., et al.
  • Journal Title: Genes Dev. 22 Pages: 1607-1616
  • Peer Reviewed
• [Journal Article] エピジェネティクス-疾患を見つめる新たな視点 (2008)
  • Author(s): 古海弘康, ほか
  • Journal Title: BIO Clinica 23 Pages: 155-159
• [Journal Article] 遺伝か環境か? : エピジェネティクスの視点から (2008)
  • Author(s): 古海弘康, ほか
  • Journal Title: 医学のあゆみ臨床ゲノム研究-成果と課題 225 Pages: 949-953
• [Journal Article] ゲノムインプリンティング (2008)
  • Author(s): 平澤竜太郎, ほか
  • Journal Title: 生体の科学(増大特集)現代医学・生物学の仮説・学説2008 59 Pages: 402-403
• [Journal Article] Epigenetic events in mammalian germ-cell development: reprog ramming and beyond. (2008)
  • Author(s): Sasaki, H. & Matsui, Y.
  • Journal Title: Nat. Rev. Genet. 9 Pages: 129-140
  • Peer Reviewed
• [Journal Article] Cohesin mediates transcriptional insulation by CCCTC-binding factor. (2008)
  • Author(s): K.S. Wendt, et. al.
  • Journal Title: Nature 451 Pages: 796-803
  • Peer Reviewed
• [Journal Article] Role of the Dnmt3 family in de novo methylation of imprinted and repetitive sequences during male germ cell development in the mouse (2007)
  • Author(s): Y. Kato, M. Kaneda, K. Hata, K. Kumaki, M. Hisano, Y. Kohara, M. Okano, E. Li, M. Nozaki, and H. Sasaki
  • Journal Title: Hum. Mol. Genet. 16 Pages: 2272-2280
  • Peer Reviewed
• [Journal Article] Aberrant DNA methylation of imprinted loci in sperm from oligospermic patients (2007)
  • Author(s): H. Kobayashi, A. Sato, E. Otsu, H. Hiura, C. Tomatsu, T. Utsunomiya, H. Sasaki, N. Yaegashi, and T. Arima
  • Journal Title: Hum. Mol. Genet. 16 Pages: 2542-2551
  • Peer Reviewed
• [Journal Article] Overlapping roles of the methylated DNA binding protein MBD1 and polycomb group proteins in transcriptional repression of HoxA genes and heterochromatin foci formation (2007)
  • Author(s): Y. Sakamoto, S. Watanabe, T. Ichimura, M. Kawasuji, H. Koseki, H. Baba, and M. Nakao
  • Journal Title: J. Biol. Chem. 282 Pages: 16391-16400
  • Peer Reviewed
• [Journal Article] The high mobility group protein HMGA1 inhibits retinoblastoma protein-mediated cellular G0 arrest (2007)
  • Author(s): Y. Ueda, S. Watanabe, S. Tei, N. Saitoh, J. Kuratsu, and M. Nakao
  • Journal Title: Cancer Sci. 98 Pages: 1893-1901
  • NAID: 10019996292
  • Peer Reviewed
• [Journal Article] Dynamic changes in the epigenomic state and nuclear organization of differentiating mouse embryonic stem cells (2007)
  • Author(s): S. Kobayakawa, K. Miike, M. Nakao, and K. Abe
  • Journal Title: Genes Cells 12 Pages: 447-460
  • Peer Reviewed
• [Journal Article] エピジェネティクスの話: 三毛猫の模様からがん治療まで (2007)
  • Author(s): 佐々木裕之, 富澤信一
  • Journal Title: ファルマシア 43 Pages: 310-314
• [Journal Article] バイサルファイト法によるDNAメチル化解析の落とし穴 (クローズアップ実験法) (2007)
  • Author(s): 佐々木裕之, 熊木健治, 小林久人, 加藤譲, 平澤竜太郎
  • Journal Title: 実験医学 25 Pages: 2191-2196
• [Journal Article] DNAメチル化を介したエピジェネティック制御機構 (2007)
  • Author(s): 日野信次朗, 渡邉すぎ子, 中尾光善
  • Journal Title: 実験医学増刊号 25 Pages: 118-123
• [Journal Article] 老化および発癌のエピジェネティクス. (2007)
  • Author(s): 丁秀鎮, 坂本快郎, 赤星慎一, 三代剛, 渡邉すぎ子, 斉藤典子, 中尾光善
  • Journal Title: 日本高齢消化器病学会誌 8 Pages: 28-37
• [Journal Article] 老化のエピジェネティクス (2007)
  • Author(s): 市村隆也, 中尾光善, 伊藤隆明
  • Journal Title: The Lung 15 Pages: 72-75
• [Journal Article] Role of the Dnmt3 family in de novo methylation of imprinted and repetitive sequences during male germ cell development in the mouse. (2007)
  • Author(s): Kato, Y., et. al.
  • Journal Title: Hum. Mol. Genet. 16 Pages: 2272-2280
  • Peer Reviewed
• [Journal Article] Aberrant DNA methylation of imprinted loci in sperm from oligospermic patients. (2007)
  • Author(s): Kobayashi, H., et. al.
  • Journal Title: Hum. Mol. Genet. 16 Pages: 2542-2551
  • Peer Reviewed
• [Journal Article] Overlapping roles of the methylated DNA binding protein MBD1 and polycomb group proteins in transcriptional repression of HoxA genes and heterochromatin foci formation. (2007)
  • Author(s): Sakamoto, Y., et. al.
  • Journal Title: J. Biol. Chem. 282 Pages: 16391-16400
  • Peer Reviewed
• [Journal Article] The high mobility group protein HMGA1 inhibits retinoblastoma protein-mediated cellular GO arrest. (2007)
  • Author(s): Ueda, Y., et. al.
  • Journal Title: Cancer Sci. 98 Pages: 1893-1901
  • Peer Reviewed
• [Journal Article] Dynamic changes in the epigenomic state and nuclear organization of differentiating mouse embryonic stem cells. (2007)
  • Author(s): Kobayakawa, S., et. al.
  • Journal Title: Genes Cells 12 Pages: 447-460
  • Peer Reviewed
• [Journal Article] エピジェネティクスの話:三毛猫の模様からがん治療まで (2007)
  • Author(s): 佐々木裕之
  • Journal Title: ファルマシア 43 Pages: 310-314
• [Journal Article] バイサルファイト法によるDNAメチル化解析の落とし穴 (2007)
  • Author(s): 佐々木裕之, ほか
  • Journal Title: 実験医学 25 Pages: 2191-2196
• [Journal Article] DNAメチル化を介したエピジェネティック制御機構 (2007)
  • Author(s): 日野信次朗, ほか
  • Journal Title: 実験医学増刊号 25 Pages: 118-123
• [Journal Article] 老化および発癌のエピジェネティクス (2007)
  • Author(s): 丁 秀鎮, ほか
  • Journal Title: 日本高齢消化器病学会誌 8 Pages: 28-37
• [Journal Article] 老化のエピジェネティクス (2007)
  • Author(s): 市村隆也, ほか
  • Journal Title: The Lung 15 Pages: 72-75
• [Journal Article] 細胞のエピジェネティクス
  • Author(s): 富澤信一, ほか
  • Journal Title: 遺伝子医学MOOK (印刷中)
• [Presentation] Epigenetic regulation and deregulation in cancer (2008)
  • Author(s): M. Nakao
  • Organizer: ortheastern Asian Symposium on Cancer Epigenetics
  • Place of Presentation: Jeju, Korea
  • Year and Date: 2008-11-07
• [Presentation] Epigenetic regulation and deregulation in cancer (2008)
  • Author(s): Nakao. M.
  • Organizer: Northeastern Asian Symposium on Cancer Epigenetics
  • Place of Presentation: Jeju, Korea
  • Year and Date: 2008-11-07
• [Presentation] Active involvement of chromatin factors in cancer epigenome (2008)
  • Author(s): 中尾光善
  • Organizer: 第65回日本癌学会総会(International Session)
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-29
• [Presentation] 生殖細胞の発生・リプログラミングとエピジェネティクス (2008)
  • Author(s): 佐々木裕之
  • Organizer: 日本人類遺伝学会第53回大会(シンポジウム)
  • Place of Presentation: 横浜
  • Year and Date: 2008-09-29
• [Presentation] エピジェネティクス機構による細胞制御と病態 (2008)
  • Author(s): 中尾光善
  • Organizer: 日本人類遺伝学会第53回大会(シンポジウム)
  • Place of Presentation: 横浜
  • Year and Date: 2008-09-29
• [Presentation] Epigenetic gene and cell regulation by chromatin factors (2008)
  • Author(s): M. Nakao
  • Organizer: The 21th Naito Conference on Nuclear dynamics and RNA [I]
  • Place of Presentation: Hokuto
  • Year and Date: 2008-06-27
• [Presentation] Epigenetic gene and cell regulation by chromatin factors (2008)
  • Author(s): Nakao. M.
  • Organizer: The 21^<th> Naito Conference on Nuclear dynamics and RNA [I]
  • Place of Presentation: Yamanashi
  • Year and Date: 2008-06-27
• [Presentation] The epigenome and small RNA repertoire in mammalian germ cells (2008)
  • Author(s): H. Sasaki
  • Organizer: International Symposium Decoding Epigenetic Code
  • Place of Presentation: Tokyo
• [Presentation] 哺乳類の生殖系列におけるゲノムインプリンティングのプログラム機構 (2008)
  • Author(s): 佐々木裕之
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会合同大会(シンポジウム)
  • Place of Presentation: 神戸
• [Presentation] クロマチン因子による遺伝子・細胞制御機構 (2008)
  • Author(s): 中尾光善
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会合同大会(シンポジウム)
  • Place of Presentation: 神戸
• [Presentation] Gametogenesis and imprinting in mice (2008)
  • Author(s): H. Sasaki
  • Organizer: EMBO Workshop on Genomic Imprinting
  • Place of Presentation: Singapore
• [Presentation] Gametogenesis and imprinting in mice. (2008)
  • Author(s): Sasaki, H.
  • Organizer: EMBO Workshop on Genomic Imprinting
  • Place of Presentation: Singapore
• [Presentation] 哺乳類の生殖細胞系列におけるゲノムインプリンティングのプログラム機構 (2008)
  • Author(s): 佐々木裕之
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会大会合同大会(シンポジウム)
  • Place of Presentation: 神戸
• [Presentation] 細胞異型の成立を探る:がんのエピジェネティクスと核内構造 (2007)
  • Author(s): 中尾光善
  • Organizer: 第46回日本臨床細胞学会秋季大会(特別講演)
  • Place of Presentation: 仙台
  • Year and Date: 2007-12-01
• [Presentation] 細胞異型の成立を探る:がんのエピジェネティクスと核内構造. (2007)
  • Author(s): 中尾光善
  • Organizer: 第46回日本臨床細胞学会秋期大会(特別講演)
  • Place of Presentation: 仙台
  • Year and Date: 2007-12-01
• [Presentation] Epigenomics in reproduction and development (2007)
  • Author(s): H. Sasaki
  • Organizer: The Asian Network of Epigenomics: Epigenomics: Technology, Products, and Obstacles
  • Place of Presentation: Suita
  • Year and Date: 2007-06-14
• [Presentation] Epigenomics in reproduction and development (2007)
  • Author(s): Sasaki, H.
  • Organizer: The Asian Network of Epigenomics 「Epigenomics: Technology, Products, and Obstacles」
  • Place of Presentation: Suita
  • Year and Date: 2007-06-14
• [Presentation] 細胞核ドメインと遺伝子発現の調節 (2007)
  • Author(s): 斉藤典子, ほか
  • Organizer: 第40回日本細胞生物学会・第59回日本発生生物学会合同年会(シンポジウム:細胞核内シグナル伝達と遺伝子発現)
  • Place of Presentation: 福岡
  • Year and Date: 2007-05-28
• [Presentation] エピジェネティクスから見た遺伝学 (2007)
  • Author(s): 佐々木裕之
  • Organizer: 第14回日本遺伝子診療学会大会
  • Place of Presentation: 松山
• [Presentation] エピジェネティクスから見た遺伝学 (2007)
  • Author(s): 佐々木裕之
  • Organizer: 第14回日本遺伝子診療学会大会「遺伝子診断による個別化医療を目指して」
  • Place of Presentation: 松山
• [Presentation] 流産のエピゲノム解析 (2007)
  • Author(s): 秦健一郎, ほか
  • Organizer: 第52回人類遺伝学会「ゲノム解析から臨床応用へのロードマップ」
  • Place of Presentation: 東京
• [Presentation] 男性不妊症の精子におけるインプリント異常 (2007)
  • Author(s): 小林久人, ほか
  • Organizer: 第30回日本分子生物学会
  • Place of Presentation: 横浜
• [Book] エピジェネティクスと疾患. 小児内科増刊号(小児疾患診療のための病態生理1, 第4版) (30-35) (2008)
  • Author(s): 中尾光善
  • Total Pages: 1574
  • Publisher: 東京医学社
• [Book] DNAメチル化と転写制御機構. 転写制御とエピジェネティクス(The Frontiers in Medical Sciences, 加藤茂明編) (91-98) (2008)
  • Author(s): 日野信次朗, 中尾光善
  • Total Pages: 237
  • Publisher: 南山堂
• [Book] 小児内科増刊号(小児疾患診療のための病態生理1、第4版) (2008)
  • Author(s): 中尾光善
  • Publisher: 東京医学社
• [Remarks] ホームページ
  • URL: http://www.nig.ac.jp/labs/HumGen/index.html
• [Remarks] ホームページ
  • URL: http://www.imeg.kumamoto-u.ac.jp
• [Remarks]
  • URL: http://www.nig.ac.jp/labs/HumGen/index.html