The mechanism for endothelial cell-specific gene expression through the Robo4 promoter.

• Project/Area Number: 20790064
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Biological pharmacy
• Research Institution: Osaka University
• Principal Investigator: OKADA Yoshiaki Osaka University, 大学院・薬学研究科, 助教 (50444500)
• Project Period (FY): 2008 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2008: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 遺伝子発現制御 / 血管内皮細胞 / Robo4遺伝子 / 組織特異的遺伝子発現 / DNAメチル化 / 組織特異性 / Hprtターゲティング法

Research Abstract

To investigate the mechanism for endothelial cell-specific gene expression, the function of regulatory elements in the ROBO4 promoter were analyzed using transgenic mice. The results indicated that both regulatory elements (REn and ETS) in the upstream and proximal promoter region were contributed to the promoter activity, and that 300bp proximal promoter region was responsible for endothelial cell-specific gene expression. In addition, the study on adenovirus vector containing ROBO4 promoter-luciferase sequence demonstrated that the ROBO4 promoter maintained endothelial cell -specificity in adenovirus.

Research Products

• [Journal Article] in vitroとin vivoで異なるレポータージーンアッセイの結果 (2010)
  • Author(s): 岡田欣晃、土井健史
  • Journal Title: 生産と技術 62巻 Pages: 51-56
  • NAID: 40017231022
• [Journal Article] in vitroとin vivoで異なるレポータージーンアッセイの結果 (2010)
  • Author(s): 岡田欣晃
  • Journal Title: 生産と技術 62 Pages: 51-56
  • NAID: 40017231022
• [Journal Article] Differential roles for ETS, CREB and EGR binding sites in mediating VEGF receptor 1 expression in vivo (2009)
  • Author(s): E. Jin, J. Liu, J. Suehiro, L. Yaun, Y. Okada, V. Nikolova-Krstevski, K. Yano, L. Janes, D. Beeler, K.C. Spokes, D. Li, E. Regan, S.C. Shih, P. Oettgen, T. Minami, W.C. Aird
  • Journal Title: Blood Vol.114 Pages: 5557-5566
  • Peer Reviewed
• [Journal Article] A +220 GATA motif mediates basal but not endotoxin-repressible expression of the von Willebrand factor promoter in Hprt-targeted transgenic mice (2009)
  • Author(s): J. Liu, Y. Kanki, Y. Okada, E. Jin, K. Yano, S. -C. Shih, T. Minami, W.C. Aird
  • Journal Title: J. Thromb. Haemost. Vol.7 Pages: 1384-1392
  • Peer Reviewed
• [Journal Article] Down's syndrome suppression of tumour growth and the role of the calcineurin inhibitor DSCR1 (2009)
  • Author(s): K.H. Baek, A. Zaslavsky, R.C. Lynch, C. Britt, Y. Okada, R.J. Siarey, M.W. Lensch, I.H. Park, S.S. Yoon, T. Minami, J.R. Korenberg, J. Folkman, G.Q. Daley, W.C. Aird, Z. Galdzicki, S. Ryeom
  • Journal Title: Nature Vol.459 Pages: 1126-1130
  • Peer Reviewed
• [Journal Article] 血管内皮細胞の遺伝子発現制御研究からみたin vivoプロモーター解析の重要性 (2009)
  • Author(s): 岡田欣晃、土井健史
  • Journal Title: 生化学 81巻 Pages: 117-121
  • NAID: 10024915912
• [Journal Article] 血管内皮細胞の遺伝子発現制御研究からみたin vivoプロモーター解析の重要性 (2009)
  • Author(s): 岡田欣晃
  • Journal Title: 生化学 81 Pages: 117-121
  • NAID: 10024915912
  • Peer Reviewed
• [Journal Article] Down's syndrome suppression of tumour growth and the role of the calcineurin inhibitor DSCR1 (2009)
  • Author(s): Kwan-Hyuck Baek
  • Journal Title: Nature 459 Pages: 1126-1130
  • Peer Reviewed
• [Journal Article] A +220 GATA motif mediates basal but not endotoxin-repressible expression of the von Willebrand factor promoter in Hprt-targeted transgexuc mice (2009)
  • Author(s): Ju Liu
  • Journal Title: Journal of thrombosis and haemostasis 284 Pages: 22195-22205
  • Peer Reviewed
• [Journal Article] Differential roles for ETS, CREB and EGR binding sites in methatine VEGF receptor 1 expression in vivo (2009)
  • Author(s): Enjing Jin
  • Journal Title: Blood 114 Pages: 5557-5566
  • Peer Reviewed
• [Journal Article] Elevated levels of placental growth factor represent an adaptive host response in sepsis (2008)
  • Author(s): K. Yano, Y. Okada, G. Beldi, S.C. Shih, N. Bodyak, H. Okada, P.M. Kang, W. Luscinskas, S.C. Robson, P. Carmeliet, S.A. Karumanchi, W.C. Aird
  • Journal Title: J Exp Med. Vol.205 Pages: 2623-2631
  • Peer Reviewed
• [Journal Article] A GABP-binding element in the Robo4 promoter is necessary for endothelial expression in vivo (2008)
  • Author(s): Y. Okada, E. Jin, V. Nikolova-Krstevski, K. Yano, J. Liu, D. Beeler, K. Spokes, M. Kitayama, N. Funahashi, T. Doi, L. Janes, T. Minami, P. Oettgen, W.C. Aird
  • Journal Title: Blood Vol.112 Pages: 2336-2339
  • Peer Reviewed
• [Journal Article] Ligand-independent assembly of purified soluble magic roundabout (Robo4), a tumor-specific endothelial marker (2008)
  • Author(s): M. Yoshikawa, Y. Mukai, Y. Okada, Y. Yoshioka, S. Tsunoda, Y. Tsutsumi, N. Okada, W.C. Aird, T. Doi, S. Nakagawa
  • Journal Title: Protein Expr Purif. Vol.61 Pages: 78-82
  • Peer Reviewed
• [Journal Article] Ligand-independent assembly of purified soluble magic roundabout (Robo4), a tumor-specific endothelial marker (2008)
  • Author(s): Yoshikawa M, Mukai Y, Okada Y, Yoshioka Y, Tsunoda S, Tsutsumi Y, Okada N, Aird WC, Doi T, Nakagawa S.
  • Journal Title: Protein Expr Purif 61 Pages: 78-82
  • Peer Reviewed
• [Journal Article] A GABP-binding element in the Robo4 promoter is necessary for endothelial expression in vivo (2008)
  • Author(s): Okada Y, Jin E, Nikolova-Krstevski V, Yano K, Liu J, Beeler D, Spokes K, Kitayama M, Funahashi N, Doi T, Janes L, Minami T, Oettgen P, Aird WC.
  • Journal Title: Blood 112 Pages: 2336-9
  • Peer Reviewed
• [Journal Article] Elevated levels of placental growth factor represent an adaptive host response in sepsis (2008)
  • Author(s): Yano K, Okada Y, Beldi G, Shih SC, Bodyak N, Okada H, Kang PM, Luscinskas W, Robson SC, Carmeliet P, Karumanchi SA, Aird WC.
  • Journal Title: J Exp Med 205 Pages: 2623-31
  • Peer Reviewed
• [Presentation] ROBO4の血管内皮細胞特異的発現制御とDNAメチル化の関連性の解析 (2010)
  • Author(s): 加納義浩, 舟橋伸昭, 成瀬啓樹, 蒋志 侠, 鈴木綾乃, 岡田欣晃, 土井健史
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山桃太郎アリーナ(岡山県)
  • Year and Date: 2010-03-30
• [Presentation] 血管内皮細胞特異的に発現するレセプターROBO4とSLITの相互作用解析 (2010)
  • Author(s): 蒋志侠, 鈴木綾乃, 舟橋伸昭, 加納義浩, 成瀬啓樹, 岡田欣晃, 土井健史
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山桃太郎アリーナ(岡山県)
  • Year and Date: 2010-03-30
• [Presentation] Robo4遺伝子の血管内皮細胞特異的な発現とDNAメチル化との関連 (2009)
  • Author(s): 舟橋伸昭、成瀬啓樹、加納義浩、Jiang Zhixia、鈴木綾乃, 岡田欣晃、土井健史
  • Organizer: 第8回次世代を担う若手ファーマバイオフォーラム2009
  • Place of Presentation: 名古屋市立大学田辺通キャンパス(愛知県)
  • Year and Date: 2009-11-14
• [Presentation] Robo4遺伝子の血管内皮細胞特異的な発現とDNAメチル化との関連 (2009)
  • Author(s): 舟橋伸昭
  • Organizer: 第8回次世代を担う若手ファーマバイオフオーラム2009
  • Place of Presentation: 名古屋市立大学田辺通キャンパス(愛知県)
  • Year and Date: 2009-11-14
• [Presentation] 血管内皮細胞に特異的に発現するRobo4遺伝子の新規転写調節配列の同定と解析 (2009)
  • Author(s): 成瀬啓樹、蒋志侠、舟橋伸昭、加納義浩、鈴木綾乃、William Aird、岡田欣晃、土井健史
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸ポートアイランド(兵庫県)
  • Year and Date: 2009-10-23
• [Presentation] Robo4プロモーターに存在するGABP結合配列のin vivoにおける重要性 (2009)
  • Author(s): 岡田欣晃、金恩京、北山美絵、舟橋伸昭、矢野喜一郎、William Aird、土井健史
  • Organizer: 第10回Pharmaco-Hematologyシンポジウム
  • Place of Presentation: 日本薬学会長井記念ホール(東京都)
  • Year and Date: 2009-06-20
• [Presentation] 血管内皮細胞に発現するレセプターROBO4のリガンドの同定 (2009)
  • Author(s): 蒋志侠, 舟橋伸昭, 加納義浩, 成瀬啓樹, 岡田欣晃, 土井健史
  • Organizer: 日本薬学会第129年会
  • Place of Presentation: 京都
  • Year and Date: 2009-03-27
• [Presentation] 血管内皮細胞と非血管内皮細胞におけるROBO4プロモーターのメチル化パターンの相違 (2009)
  • Author(s): 加納義浩、舟橋伸昭、成瀬啓樹、蒋志 侠、岡田欣晃、土井健史
  • Organizer: 日本薬学会第129年会
  • Place of Presentation: 京都
  • Year and Date: 2009-03-26
• [Presentation] 血管内皮細胞と非血管内皮細胞におけるROBO4プロモーターのDNAメチル化状態の相違 (2008)
  • Author(s): 舟橋伸昭、成瀬啓樹、加納義浩、Zhixia Jiang、岡田欣晃、土井健史
  • Organizer: 第81回日本生化学会大会第31回日本分子生物学会年会合同大会(BMB2008)
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-11
• [Presentation] 新規血管内皮細胞マーカーRobo4のi n vivo発現制御機構解析 (2008)
  • Author(s): 岡田欣晃、金恩京、北山美絵、舟橋伸昭、矢野喜一郎、William Aird、土井健史
  • Organizer: 第81回日本生化学会大会第31回日本分子生物学会年会合同大会(BMB2008)
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-11
• [Presentation] 新規血管内皮細胞マーカーRobo4のin vivo発現制御機構解析 (2008)
  • Author(s): 岡田欣晃、金恩京、北山美絵、舟橋伸昭、矢野喜一郎、William Aird、土井健史
  • Organizer: 第81回日本生化学会大会第31回日本分子生物学会年会合同大会(BMB2008)
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-11
• [Presentation] Difference of the methy lation pattern of the Robo4 promoter bet ween endothelial cell and non-endothelial cell (2008)
  • Author(s): Yoshiaki Okada, Nobuaki Funahashi, Yos hihiro Kano, Hiroki Naruse, Zhixia Jiang, Enjing Jin, Kiichiro Yano, William Aird, Takefumi Doi
  • Organizer: The 6th Korea-Japan Joint Symposiu m on Vascular Biology and The 16th A nnual Meeting of the Japan Vascular Bio logy and Medicine Organization JOINTM EETING
  • Place of Presentation: 金沢
• [Presentation] Difference of the methylation pattern of the Robo4 promoter between endothelial cell and non-endothelial cell (2008)
  • Author(s): Yoshiaki Okada, Nobuaki Funahashi, Yoshihiro Kano, Hiroki Naruse, Zhixia Jiang, Enjing Jin, kiichiro Yano, William Aird, Takefumi Doi
  • Organizer: The 6^<th> Korea-Japan Joint Symposium on Vascular Biology and The 16th Annual Meeting of the Japan Vascular Biology and Medicine Organization JOINT MEETING
  • Place of Presentation: 金沢
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