Analysis of AID expression by a novel Cre-based in vivo gene manipulation system.

• Project/Area Number: 23659151
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: General medical chemistry
• Research Institution: Gifu University
• Principal Investigator: NAGAOKA Hitoshi 岐阜大学, 医学(系)研究科(研究院), 教授 (20270647)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: リンパ球分化 / 免疫 / 遺伝子 / 発現制御 / リンパ球 / 遺伝子組換え / 転写因子 / 細胞分化 / 生体分子医学 / ゲノム医科学

Research Abstract

We studied the Aicda (activation-induced cytidine deaminase's gene) gene regulation in vivo by using Aicda-cre BAC transgenic system. We found that the Aicda gene is expressed in some mature T cells in periphery in addition to the germinal center B cells. The AID expression associated with the development of a IL-10-producing subset of CD4 T cells, that indicates some specific stimuli may be operating for induction of AID. The manipulations of cis regulatory elements of Aicda on the transgenes revealed that indispensable role of C/EBP binding sites in the upstream region for AID expression, and the silencer activity of intronic E2F and Myb binding sites. These results provide a important information to understanding spatiotemporal regulation of Aicda gene.

Research Products

• [Journal Article] Mitotic catastrophe and cell deathinduced by depletion of centrosomalproteins (2013)
  • Author(s): Kimura, M., Yoshioka, T., Saio, M.,Banno, Y., Nagaoka, H., and Okano, Y
  • Journal Title: Cell Death Dis Volume: 4 Issue: 4 Pages: e603-e603
  • DOI: 10.1038/cddis.2013.108
  • Peer Reviewed
• [Journal Article] In vivo analysis of Aicda gene regulation: a critical balance between upstream enhancers and intronic silencers governs appropriate expression (2013)
  • Author(s): Le Thi Huong, Maki Kobayashi,et al
  • Journal Title: PLoSONE Volume: vol.8 Issue: 4 Pages: e61433-e61433
  • DOI: 10.1371/journal.pone.0061433
  • Peer Reviewed
• [Journal Article] The AID Dilemma: Infection, or Cancer? (2013)
  • Author(s): Tasuku Honjo, Maki Kobayashi, Nasim Begum, Ai Kotani, Somayeh Sabour and Hitoshi Nagaoka
  • Journal Title: Adv Cancer Res Volume: vol.113 Pages: 1-44
  • DOI: 10.1016/b978-0-12-394280-7.00001-4
  • Peer Reviewed
• [Journal Article] Identification of a Rho family specificguanine nucleotide exchange factorFLJ00018, as a novel actin-bindingprotein (2013)
  • Author(s): Sato, K., Handa, H., Kimura, M., Okano,Y., Nagaoka, H., Nagase, T., Sugiyama,T., Kitade, Y., and Ueda, H.
  • Journal Title: Cell. Signal. Volume: 25 Issue: 1 Pages: 41-49
  • DOI: 10.1016/j.cellsig.2012.09.015
  • Peer Reviewed
• [Journal Article] Imatinib mesylate directly impairs class switch recombination through downregulation of AID. (2012)
  • Author(s): Kawamata T, Lu J, Sato T, Tanaka M, Nagaoka H, Agata Y, Toyoshima T, Yokoyama K, Oyaizu N, Nakamura N, Ando K, Tojo A, Kotani A
  • Journal Title: Blood Volume: 119 Issue: 13 Pages: 3123-3127
  • DOI: 10.1182/blood-2011-01-327932
  • Peer Reviewed
• [Journal Article] Activation-Induced Cytidine Deaminase Expression in CD4 T Cells is Associated with a Unique IL-10-Producing Subset that Increases with Age (2011)
  • Author(s): Qin, H., 他
  • Journal Title: PLoS One Volume: 6(電子出版) Issue: 12 Pages: e29141-e29141
  • DOI: 10.1371/journal.pone.0029141
  • Peer Reviewed
• [Journal Article] Histone chaperone Spt6 is required for class switch recombination but not somatic hypermutation (2011)
  • Author(s): Okazaki IM, Okawa K, Kobayashi M, Yoshikawa K, Kawamoto S, Nagaoka H, Shinkura R, Kitawaki Y, Taniguchi H, Natsume T, Iemura S, and Honjo T
  • Journal Title: Proc Natl Acad Sci USA Volume: 108 Issue: 19 Pages: 920-925
  • DOI: 10.1073/pnas.1104423108
  • NAID: 120003163668
  • Peer Reviewed
• [Presentation] Rho 活性化因子FLJ00018 とFour and Half LIM domain 1との相互作用 (2013)
  • Author(s): 佐藤克哉, 他
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: 横浜市
  • Year and Date: 2013-09-12
• [Presentation] In vivo analysis of Aicda gene regulation : critical balance between upstream enhancer and intronic repressor for the appropriate expression (2013)
  • Author(s): Nagaoka, H., et al.
  • Organizer: 15th International Congress of Immunology
  • Place of Presentation: Milan, Italy
  • Year and Date: 2013-08-25
• [Presentation] In vivo analysis of Aicda gene regulation: critical balance between upstream enhancer and intronic repressor for the appropriate expression. (2013)
  • Author(s): L. Huong, M. Kobayashi, M. Nakata, G. Shioi, H. Miyachi, T. Honjo, H. Nagaoka
  • Organizer: 15th international congress of immunology
  • Place of Presentation: Milan, Italy
• [Presentation] n vivo analysis of Aicda gene regulation: critical balance between upstream enhancer and intronic repressor for the appropriate expression (2013)
  • Author(s): L. Huong, M. Kobayashi, M. Nakata, G. Shioi, H. Miyachi, T. Honjo, H. Nagaoka
  • Organizer: 15th International Congress of Immunology
  • Place of Presentation: Milan, Italy
• [Presentation] Rho 特異的活性化因子FLJ00018 とアクチンの相互作用によるFLJ00018 の機能抑制 (2012)
  • Author(s): 佐藤克哉, 他
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡市
  • Year and Date: 2012-12-16
• [Presentation] Activation-induced cytidine deaminase expression in CD4+ T cells is associated with a unique IL- 10-producing subset that increases with age (2012)
  • Author(s): Nagaoka, H, et al.
  • Organizer: Genetic and Epigenetic Control of Cell Fate
  • Place of Presentation: 京都市
  • Year and Date: 2012-11-06
• [Presentation] Activation-induced cytidine deaminase expression in CD4+ T cells is associated with a unique IL-10-producing subset that increases with age (2012)
  • Author(s): Hongyan Qin, Keiichiro Suzuki, Mikiyo Nakata, Shunsuke Chikuma, Nakako Izumi, Le Thi Huong, Mikako Maruya, Sidonia Fagarasan, Meinrad Busslinger, Tasuku Honjo and Hitoshi Nagaoka
  • Organizer: Genetic and Epigenetic Control of Cell Fate
  • Place of Presentation: 京都市
• [Presentation] AID 遺伝子が発現するT細胞サブセットはIL-10 を発現し加齢とともに蓄積するユニークなサブセットである (2011)
  • Author(s): 長岡 仁, 他
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都市
  • Year and Date: 2011-09-24
• [Presentation] RNF8 によるPlk1 タンパク質の減少とがん細胞における異常 (2011)
  • Author(s): 吉岡 孝, 他
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都市
  • Year and Date: 2011-09-22
• [Presentation] AID遺伝子が発現するT細胞サブセットはIL-10を発現し加齢とともに蓄積するユニークなサブセットである
  • Author(s): 長岡 仁. 他
  • Organizer: 第８４回日本生化学会大会
  • Place of Presentation: 京都市
• [Presentation] RNF8によるPlk1タンパク質の減少とがん細胞における異常
  • Author(s): 吉岡 孝 他
  • Organizer: 第８４回日本生化学会大会
  • Place of Presentation: 京都市
• [Remarks]
  • URL: http://www.med.gifu-u.ac.jp/labo/labo-j/molpathobiochem.html