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

2013 Fiscal Year Final Research Report

• 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
• Keywords: リンパ球分化 / 免疫

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 death induced by depletion of centrosomal proteins (2013)
  • Author(s): Kimura, M, Yoshioka, T, Saio, M, Banno,Y, Nagaoka, H, Okano, Y
  • Journal Title: Cell Death Dis Volume: 4 Pages: 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): Huong le, T, Kobayashi, M, Nakata, M, Shioi, G, Miyachi, H, Honjo, T, Nagaoka, H
  • Journal Title: PLoS One Volume: 8 Pages: e61433
  • DOI: 10.1371/journal.pone.0061433
  • Peer Reviewed
• [Journal Article] The AID Dilemma : Infection, or Cancer? (2012)
  • Author(s): Honjo, T, Kobayashi, M, Begum, N, Kotani, A, Sabouri, S, Nagaoka, H
  • Journal Title: Adv Cancer Res Volume: 113 Pages: 1-44
  • DOI: 10.1016/B978-0-12-394280-7.00001-4
• [Journal Article] Imatinib mesylate directly impairs class switch recombination through down-regulation of AID : its potential efficacy as an AID suppressor (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 Pages: 3123-7
  • DOI: 10.1182/blood-2011-01-327932
  • Peer Reviewed
• [Journal Article] Identification of a Rho family specific guanine nucleotide exchange factor, FLJ00018, as a novel actin-binding protein (2012)
  • Author(s): Sato, K, Handa, H, Kimura, M, Okano, Y, Nagaoka, H, Nagase, T, Sugiyama, T, Kitade, Y, Ueda, H
  • Journal Title: Cell Signal Volume: 25 Pages: 41-9
  • DOI: 10.1016/j.cellsig.2012.09.015
  • 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, Suzuki, K, Nakata, M, Chikuma, S, Izumi, N, Thi Huong, L, Maruya, M, Fagarasan, S, Busslinger, M, Honjo, T, Nagaoka, H
  • Journal Title: PLoS One Volume: 6 Pages: e29141
  • DOI: 10.1371/journal.pone.0029141
  • 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] 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] 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