Mechanism of lineage commitment by GATA3 - RNA polymeraseII, FACT complex and DNA demethylation

• Project/Area Number: 19590296
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Tokyo Metropolitan Organization for Medical Research
• Principal Investigator: MIYATAKE Shoichiro Tokyo Metropolitan Organization for Medical Research, 東京都臨床医学総合研究所, 副参事研究員 (30239420)
• Co-Investigator(Kenkyū-buntansha): AOKI Kazuhisa 財団法人東京都医学研究機構, 東京都臨床医学総合研究所, 研究員 (00280785) ; SATO Noriko 東京医科歯科大学, 難治疾患研究所・分子疫学分野, 准教授 (70280956)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2007: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: FACT / GATA3 / DNAメチル化 / Th1 / Th2 / DNA メチルトランスフェラーゼ / DNAメチルトランスフェラーゼ

Research Abstract

寄生虫感染に対する生体防御やアレルギー疾患に関与するTh2細胞の分化について、マスターレギュレーターGATA3の作用機序を解析した。GATA3は転写を担うRNAポリメラーゼIIおよびFACT複合体を染色体へ運ぶ機能を持つことが示唆された。またサイトカイン遺伝子の発現制御にはDNA脱メチル化が重要で、T細胞の分化過程においてその活性が変化する事、DNA複製非依存的であること、メチルシトシン結合タンパク質が関与する事などを明らかにした。

Research Products

• [Journal Article] T-box 21 transcription factor is responsible for distorted T(H)2 differentiation in human peripheral CD4+ T cells. (2009)
  • Author(s): Kaminuma, O., Kitamura, F., Miyatake, S., Yamaoka, K., Miyoshi, H., Inokuma, S., Tatsumi, H., Nemoto, S., Kitamura, N., Mori, A., and Hiroi, T.
  • Journal Title: J. Allergy Clin. Immunol. 123
  • Peer Reviewed
• [Journal Article] Ly49Q ligand expressed by activated B cells induces plasmacytoid DC maturation. (2009)
  • Author(s): Toma-Hirano, M., Namiki, S., Shibata, Y., Ishida, K., Arase, H., Miyatake, S., Arai, K. and Kamogawa-Schifter, Y.
  • Journal Title: Eur. J. Immunol. 39 Pages: 1344-52
  • Peer Reviewed
• [Journal Article] Regulation of DNA demethylation during maturation of CD4+ naive T cells by the conserved non-coding sequence CNS-1 (2009)
  • Author(s): Aoki, K., Sato, N., Yamaguchi, A., Kaminuma, O., Hosozawa, T., Miyatake, S
  • Journal Title: The Journal of Immunology (印刷中)
  • Peer Reviewed
• [Journal Article] Airway eosinophilic inflammation is attenuated in conserved noncoding sequence-1 deficient mice. (2008)
  • Author(s): Ohtomo, T., Miyatake, S., Kajiyama, Y., Umezu-Gotoa, M., Kaminuma, O. and Mori, A.
  • Journal Title: Int. Arch. Allergy Immunol. 146 Suppl 1 Pages: 2-6
  • Peer Reviewed
• [Journal Article] Cyclic AMP-induced chromatin changes support the NFATc-mediated recruitment of GATA-3 to the interleukin 5 promoter. (2008)
  • Author(s): Klein-Hessling, S., Bopp, T., Jha, M.K., Schmidt, A., Miyatake, S., Schmitt, E. and Serfling, E.
  • Journal Title: J. Biol. Chem. 283 Pages: 31030-7
  • Peer Reviewed
• [Journal Article] The role of CD11b in phagocytosis and dendritic cell development. (2008)
  • Author(s): Chen, J., Namiki, S., Toma-Hirano, M., Miyatake, S., Ishida, K., Shibata, Y., Arai, N., Arai, K., and Kamogawa-Schifter, Y.
  • Journal Title: Immunol. Lett. 120 Pages: 42-48
  • Peer Reviewed
• [Journal Article] Downregulation of IL-13 gene transcription by T-bet in human T cells. (2008)
  • Author(s): Suzuki, K., Kaminuma, O., Hiroi, T., Kitamura, F., Miyatake, S., Takaiwa, F., Tatsumi, H., Nemoto, S., Kitamura, N. and Mori, A.
  • Journal Title: Int. Arch. Allergy Immunol. 146 Suppl 1 Pages: 33-5
  • Peer Reviewed
• [Journal Article] Differential Contribution of NFATc2 and NFATc1 to TNF-α Gene Expression in T Cells. (2008)
  • Author(s): Kaminuma, O., Kitamura, F., Kitamura, N., Hiroi, T., Miyoshi, H., Miyawaki, A., Miyatake, S.
  • Journal Title: J. Immunol. 180 Pages: 1319-26
  • Peer Reviewed
• [Journal Article] Differential Contribution of NFATc2 and NFATc1 to TNF-α Gene Expression in T Cells (2008)
  • Author(s): Kaminuma O, Kitamura F, Kitamura N, Hiroi T, Miyoshi H, Miyawaki A, Miyatake S
  • Journal Title: The Journal of Immunology 180 Pages: 1319-26
  • Peer Reviewed
• [Journal Article] Cyclic AMP-induced chromatin changes support the NFATc-mediated recruitment of GATA-3 to the interleukin 5 promoter (2008)
  • Author(s): Klein-Hessling, S., Bopp, T., Jha, M. K., Schmidt, A., Miyatake, S., Schmitt, E. Serfling, E
  • Journal Title: The Journal of Biological Chemistry 283 Pages: 31030-7
  • Peer Reviewed
• [Journal Article] (2008)
  • Author(s): 青木和久, 宮武昌一郎
  • Journal Title: Th2分化制御メカニズム細胞工学(秀潤社)
• [Journal Article] (2008)
  • Author(s): 青木和久, 宮武昌一郎
  • Journal Title: サイトカイン遺伝子におけるクロマチン制御機構 臨床免疫・アレルギー科(科学評論社)
• [Journal Article] Differential Contribution of NFATc2 and NFATc1 to TNF-α Gene Expression in T Cells. (2008)
  • Author(s): Kaminuma O., Kitamura F., Kitamura N., Hiroi T., Miyoshi H., Miyawaki A., Miyatake S
  • Journal Title: The Journal of Immunology 180 Pages: 1319-1326
  • Peer Reviewed
• [Journal Article] Type I interferon regulates pDC maturation and Ly49Q expression. (2007)
  • Author(s): Toma-Hirano, M., Namiki, S., Miyatake, S., Arai, K. and Kamogawa-Schifter, Y.
  • Journal Title: Eur. J. Immunol. 37 Pages: 2707-14
  • Peer Reviewed
• [Journal Article] IL-4 gene transcription in human T cells is suppressed by T-bet. Int. Arch. (2007)
  • Author(s): Kitamura, N., Kitamura, F., Kaminuma, O., Miyatake, S., Tatsumi, H., Nemoto, S. and Mori, A.
  • Journal Title: Allergy Immunol. 143 Suppl Pages: 68-70
  • Peer Reviewed
• [Journal Article] Regulation of DNA demethylation during maturation of CD4+ naive T cells by the conserved non-coding sequence CNS-1.
  • Author(s): Aoki, K., Sato, N., Yamaguchi, A., Kaminuma, O., Hosozawa, T. and Miyatake, S.
  • Journal Title: J. Immunol. (印刷中) Pages: 0-0
  • Peer Reviewed
• [Presentation] T細胞サイトカイン産生における脱メチル化制御の役割 (2008)
  • Author(s): 宮武昌一郎、青木和久
  • Organizer: 第18回kyoto T cell Conference
  • Place of Presentation: 京都
• [Presentation] Different cytokine expression and DNA demethylation profiles between CD4 single positive thymocytes and peripheral naive T cells. (2008)
  • Author(s): Aoki, K. and Miyatake, S.
  • Organizer: The 38th Annual Meeting of the Japanese Society for Immunology
  • Place of Presentation: Kyoto
• [Presentation] C-terminal transactivation domain is required for NFAT-mediated TNF-alpha synthesis by T cells. (2008)
  • Author(s): Kaminuma, O., Kitamura, F., Kitamura, N., Miyatake, S., Hiroi, T.
  • Organizer: The 38th Annual Meeting of the Japanese Society for Immunology
  • Place of Presentation: Kyoto
• [Presentation] 胸腺と末梢のCD4陽性T細胞におけるサイトカイン発現パターンの差異はDNA脱メチル化制御の差異による (2008)
  • Author(s): 青木和久、宮武昌一郎
  • Organizer: 第31回日本分子生物学会年会
  • Place of Presentation: 神戸
• [Presentation] T細胞サイトカイン産生における脱メチル化制御の役割 (2008)
  • Author(s): 青木和久, 宮武昌一郎
  • Organizer: 第18回 kyoto T cell Conference
  • Place of Presentation: 京都
• [Presentation] Different cytokine expression and DNA demethylation profiles between CD4 single positive thymocytes and peripheral naive T cells (2008)
  • Author(s): 青木和久, 宮武昌一郎
  • Organizer: The 38th Annual Meeting of the Japanese Society for Immunology
  • Place of Presentation: 京都
• [Presentation] アレルギー学の基礎 (2007)
  • Author(s): 宮武昌一郎
  • Organizer: 第31回専門医教育セミナープログラム 日本アレルギー学会
  • Place of Presentation: 横浜
  • Year and Date: 2007-06-12
• [Presentation] サイトカイン遺伝子領域における複製開始点および複製タイミングの解析 (2007)
  • Author(s): 宮武昌一郎、尾田真子、佐藤憲子、青木和久、正井久雄
  • Organizer: 特定領域研究「染色体サイクルの制御ネットワーク」第3回領域会議
  • Place of Presentation: 石川県加賀
• [Presentation] Analysis of DNA demethylation coupled with CD4+ T cell subset differentiation (2007)
  • Author(s): Aoki, K. and Miyatake, S.
  • Organizer: The 37th Annual Meeting of the Japanese Society for Immunology
  • Place of Presentation: Tokyo
• [Presentation] Th2サイトカイン遺伝子領域における複製開始点および複製タイミングの解析 (2007)
  • Author(s): 宮武昌一郎、青木和久、正井久雄
  • Organizer: 第30回日本分子生物学会年会
• [Presentation] T細胞の分化に伴うDNAの脱メチル化による遺伝子発現制御 (2007)
  • Author(s): 青木和久、宮武昌一郎
  • Organizer: 第30回日本分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] Analysis of DNA demethylation coupled with CD4+Tcell subset differentiation (2007)
  • Author(s): Aoki, K..and Miyatake, S.
  • Organizer: The 37th Annual Meeting of the Japanese Society for Immunology
  • Place of Presentation: Tokyo
• [Book] Th2分化制御メカニズム 細胞工学「T細胞サブセット : どこまで感染症や免疫疾患との関わりが理解されてきたのか?」 (2008)
  • Author(s): 青木和久、宮武昌一郎
  • Publisher: 秀潤社
• [Book] サイトカインのエピゲネティック調節 臨床免疫・アレルギー科 (2008)
  • Author(s): 青木和久、宮武昌一郎
  • Publisher: 科学評論社
• [Remarks]
  • URL: http://www.rinshoken.or.jp/I/