Studies on the mechanism of tissue-specific modulation of AhR-dependent gene expression

• Project/Area Number: 21790565
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Hygiene
• Research Institution: National Institute for Environmental Studies
• Principal Investigator: SUZUKI Takehiro National Institute for Environmental Studies, 環境健康研究領域, 研究員 (60425494)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2010: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000); Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: ダイオキシン / AhR / CYP1A1 / 臓器特異性 / CYPIAI / エピジェネティクス

Research Abstract

In this study, we investigated the mechanism of tissue-specific modulation of AhR-dependent gene expression by focusing on the transcriptional repressor in the liver and spleen. The results of this study suggested that expression of AhRR and HDACs and changes of histone modifications were involved in the tissue-specific modulation of CYP1A1 gene expression. We explored the genes which potentially regulated in AhR-dependent and XRE-independent manner in genome wide analysis of AhR binding regions using ChIP on chip, and obtained important information for understanding the mechanism responsible for tissue-specific reactivity of TCDD.

Research Products

• [Journal Article] Expression of Constitutively Active Aryl Hydrocarbon Receptor in T-Cells Enhances the Down-regulation of CD62L, But Does Not Alter Expression of CD25 or Suppress the Allogeneic CTL Response. (2009)
  • Author(s): Funatake CJ., Ao K., Suzuki T., Murai H., Yamamoto M., Fujii-Kuriyama Y., Kerkvliet NI., Nohara K.
  • Journal Title: J Immunotoxicol. 6(3) Pages: 194-203
  • Peer Reviewed
• [Journal Article] Constitutively active aryl hydrocarbon receptor expressed in T cells increases immunization-induced IFN-gamma productionin mice but does not suppress T(h)2-cytokine production or antibody production. (2009)
  • Author(s): Nohara K., Suzuki T., Ao K., Murai H., Miyamoto Y., Inouye K., Pan X., Motohashi H., Fujii-Kuriyama Y., Yamamoto M., Tohyama C.
  • Journal Title: Int Immunol. 21(7) Pages: 769-777
  • Peer Reviewed
• [Journal Article] Comparison of immunotoxicity among tetrachloro-, pentachloro-, tetrabromo- and pentabromo-dibenzo-p- dioxins in mice. (2009)
  • Author(s): Ao K., Suzuki T., Murai H., Matsumoto M., Nagai H., Miyamoto Y., Tohyama C., Nohara K.
  • Journal Title: Toxicology. 256(1-2) Pages: 25-31
  • Peer Reviewed
• [Presentation] ダイオキシン再投与によるダイオキシン標的遺伝子発現調節の臓器特異性の検討 (2010)
  • Author(s): 鈴木武博,高本沙代子,野原恵子
  • Organizer: 第80回日本衛生学会学術総会
  • Year and Date: 2010-05-10
• [Presentation] ダイオキシン再投与によるダイオキシン標的遺伝子発現調節の臓器特異性の検討 (2010)
  • Author(s): 鈴木武博
  • Organizer: 第80回日本衛生学会学術総会
  • Place of Presentation: 仙台国際センター(宮城県)
  • Year and Date: 2010-05-10
• [Presentation] ダイオキシンによるエピジェネティック修飾持続性の臓器特異性の検討 (2009)
  • Author(s): 鈴木武博,高本沙代子,野原恵子
  • Organizer: 第32回日本分子生物学会年会
  • Year and Date: 2009-12-12
• [Presentation] ダイオキシンによるエピジェネティック修飾持続性の臓器特異性の検討 (2009)
  • Author(s): 鈴木武博
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2009-12-12
• [Presentation] ダイオキシン毒性発現の臓器特異性とヒストン修飾との関連 (2009)
  • Author(s): 鈴木武博,高本沙代子,野原恵子
  • Organizer: 第3回日本エピジェネティクス研究会
  • Year and Date: 2009-05-23
• [Presentation] ダイオキシン毒性発現の臓器特異性とヒストン修飾との関連 (2009)
  • Author(s): 鈴木武博
  • Organizer: 第3回日本エピジェネティクス研究会
  • Place of Presentation: 学術総合センター(東京都)
  • Year and Date: 2009-05-23