Analysis for HNF-4-mediated transcriptional regulation in response to insulin stimulation in the liver

• Project/Area Number: 19780247
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Applied molecular and cellular biology
• Research Institution: University of Tsukuba
• Principal Investigator: HIROTA Keiko University of Tsukuba, 大学院・生命環境科学研究科, 研究員 (00375370)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,790,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥390,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥2,100,000 (Direct Cost: ¥2,100,000)
• Keywords: 転写制御 / 糖代謝 / HNF4 / FOXO1 / glucose-6-phoshatase / glucokinase / insulin / in vivo LUC assay / NHF4 / Foxol / glucose-6-phosphatase / In vivo LUC

Research Abstract

解糖系酵素・Glucokinase遺伝子の転写はインスリン存在下で活性化され、糖新生酵素・G6pase遺伝子の転写はインスリン非存在下で活性化される。これまでにHNF4がこれら2つの遺伝子の転写を活性化することが報告されていた。本研究においては、これら遺伝子のインスリン応答性転写制御におけるHNF4の役割を明らかにすることを目的に解析を行った。その結果、FOXO1とHNF4とのコンビネーションが、遺伝子依存的に相反する機能を発揮し、インスリン応答性転写制御に重要であることを明らかにした。

Research Products

• [Journal Article] A combination of HNF-4 and Foxo1 is required for reciprocal transcriptional regulation of glucokinase and glucose-6-phosphatase genes in response to fasting and feeding. (2008)
  • Author(s): Hirota, K. , Sakamaki, J. , Ishida, J. , Shimamoto, Y. , Nishihara, S. , Komada, N. , Ohta, K. , Yamamoto, M. , Tanimoto, K. , and Fukamizu, A.
  • Journal Title: J. Biol. Chem. 283 Pages: 32432-32441
  • Peer Reviewed
• [Journal Article] A combination of.HNF-4 and Foxol is required for reciprocal transcriptional regulation of glucokinase and glucose-6-phosphatase genes in response to fasting and feeding. (2008)
  • Author(s): Hirota, K., Sakamaki, J., Ishida, J., Shimamoto, Y., Nishihara ; S., Komada, N., Ohta, K., Yamamoto, M., T animoto, K., and Fukamizu, A.
  • Journal Title: J. Biol. Chem. 283 Pages: 32432-32441
  • Peer Reviewed
• [Journal Article] Bile acid represses the peroxisome proliferator-activated receptor-gamma coactivator-1 promoter activity in a small heterodimer partner-dependent manner. (2007)
  • Author(s): Hirota, K. , Yamagata K, Yoshimochi K, Daitoku H, , Fukamizu A.
  • Journal Title: Int J Mol Med. 19 Pages: 751-756
  • Peer Reviewed
• [Journal Article] Bile acid represses the peroxisome proliferator-activated receptor-gamma coactivator-1 promoter activity in a small heterodimer partner-dependent manner. (2007)
  • Author(s): Yamagata K, Yoshimochi K, Daitoku H, Hirota K, Fukamizu A.
  • Journal Title: Int J Mol Med. 19 Pages: 751-756
  • Peer Reviewed
• [Presentation] HNF4・FOXO1における絶食・摂食に応答した糖代謝遺伝子発現制御機構の解析 (2009)
  • Author(s): 廣田恵子、深水昭吉
  • Organizer: 第1回核内受容体研究会
  • Place of Presentation: 東京
  • Year and Date: 2009-03-20
• [Presentation] HMGA1によるFoxo1を介したG6Pase遺伝子発現調節機構の解明 (2009)
  • Author(s): 堺井陽香里,廣田恵子, 大徳浩照,深水昭吉
  • Organizer: 遺伝情報 DECODE・冬のワークショップ
  • Place of Presentation: 新潟
  • Year and Date: 2009-01-19
• [Presentation] 転写因子HNF4・FOXO1による糖新生・解糖系律速酵素の転写制御機構の解析 (2008)
  • Author(s): 廣田恵子、石田純治、坂巻純一、島本陽子、西原茂城、児玉典央、太田和秀、山本雅之、谷本啓司、深水昭吉
  • Organizer: 第12回日本心血管内分泌代謝学会学術総会
  • Place of Presentation: 熊本
  • Year and Date: 2008-11-29
• [Presentation] A combination of HNF-4 Foxo1 is Required for Reciprocal Transcriptional Regulation of Glucokinase and Glucose-6-phosphatase Genes in Response to fasting and feeding (2008)
  • Author(s): 廣田恵子、石田純治、島本陽子、西原茂城、児玉典央、太田和秀、山本雅之、谷本啓司、深水昭吉
  • Organizer: THE 21^<st> NAITO CONERENCE
  • Place of Presentation: 山梨
  • Year and Date: 2008-06-24
• [Presentation] A combination of HNF-4 and Foxo1 is required for reciprocal transcriptional regulation of glucokinase and glucose-6-phosphatase genes in response to fasting and feeding (2008)
  • Author(s): 廣田恵子、石田純治、山本雅之、谷本啓司、深水昭吉
  • Organizer: New Frontier for Lipid and Energy Metabolism
  • Place of Presentation: 茨城
  • Year and Date: 2008-02-18
• [Presentation] In vivo LUC assayを用いた糖代謝制御遺伝子発現調節機構の解析 (2007)
  • Author(s): 廣田恵子、石田純治、深水昭吉
  • Organizer: 第24回日本疾患モデル学会
  • Place of Presentation: つくば国際会議場
  • Year and Date: 2007-08-31
• [Remarks]
  • URL: http://akif2.tara.tsukuba.ac.jp/