Analysis of Gata1 gene transcriptional regulation

• Project/Area Number: 19770187
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Developmental biology
• Research Institution: Tohoku University
• Principal Investigator: MORIGUCHI Takashi Tohoku University, 大学院・医学系研究科, 講師 (10447253)
• 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: GATA1 / トランスジェニックマウス / BAC / 赤血球 / 白血病 / GATA-1ノックダウンマウス / ChIP on Chip解析 / エストロゲン受容体合型GATA-1 / GATA-1BAC / レトロウイルスベクター / 転写因子複合体 / エストロゲン受容体融合型GATA-1

Research Abstract

2年間の研究により以下のことを明らかにした。
1. マウスGata1遺伝子を含む196 kbの大腸菌人工染色体(BAC)にGFPを挿入した構築を用いて作成したトランスジェニックマウス(GATA1-BAC-GFPマウス)では、GFPレポーター遺伝子の発現パターンが内在性GATA1の発現パターンを忠実に再現することが明らかになった。
2. GATA1-BAC-GFPマウスでのGFP蛍光と血液細胞表面マーカーの組み合わせにより、赤血球系前駆細胞を分化段階ごとに分離する方法を確立した。
3. GATA-1ノックダウンマウス白血病細胞に由来する細胞株を用いて、Chip on ChIP解析により多くのGATA-1標的遺伝子を見いだした。
4. GATA1-BAC-GFPマウスを用いた解析から、GATA-1遺伝子の制御領域であるG1HEおよびdouble GATA領域の機能を明らかにした。
5. ヒトGATA-1BAC トランスジェニックマウスを作成し、GATA-1変異マウスの胎児致死性をレスキューすることに成功した。

Research Products

• [Journal Article] Differential Contribution of the Gata1 Gene Hematopoietic to Erythroid Differentiation (2009)
  • Author(s): Suzuki M, Moriguchi T, Ohneda K and Yamamoto M
  • Journal Title: Mol Cell Biol 29 Pages: 1163-1175
  • Peer Reviewed
• [Journal Article] Differential contribution of the Gatal gene hematopoietic enhancer to erythroid differentiation (2009)
  • Author(s): Suzuki M, Morieuchi T, Ohneda K and Yamamoto M.
  • Journal Title: Molecular and Cellular Biology 29 Pages: 1163-1175
  • Peer Reviewed
• [Journal Article] Gata1遺伝子発現制御領域の血球分化段階特異的な機能的貢献 (2009)
  • Author(s): 森口尚
  • Journal Title: 東北医学会雑誌 120 Pages: 193-196
  • NAID: 120003660438
• [Journal Article] Transcription Factor Networks SpecifySympathetic and Adrenal ChromaffinCell Differentiation (2007)
  • Author(s): Moriguchi, T, Lim, K-C, and Engel J. D.
  • Journal Title: Functional Development and Embryology 1 Pages: 130-135
  • Peer Reviewed
• [Journal Article] GATA-3 is required for definitive nephrogenesis (2007)
  • Author(s): Hasegawa SL, Moriguchi T, Rao A, Kuroha T, Grosveld F, Engel JD and Lim KC
  • Journal Title: Dev Biol 301 Pages: 568-577
  • Peer Reviewed
• [Journal Article] Transcription Factor Networks Specify Sympathetic and Adrenal Chromaffin Cell Differentiation. (2007)
  • Author(s): Moriguchi T, Lim KC and Engel JD.
  • Journal Title: Functional Development and Embryology 1 Pages: 130-135
  • Peer Reviewed
• [Journal Article] GATA-3 is required for definitive nephrogenesis. (2007)
  • Author(s): Hasegawa SL, Moriguchi T, Rao A, Kuroha T, Grosveld F, Engel JD and Lim KC.
  • Journal Title: Developmental Biology 301 Pages: 568-577
  • Peer Reviewed
• [Journal Article] c-Maf is essential for F4/80 expression in macrophages
  • Author(s): Nakamura M, Hamada M, Kusakabe M, Hasegawa K, Suzuki H, Greaves, DR, Moriguchi T, Kudo T, Takahahi S.
  • Journal Title: in vivo. Gene (in press)
  • Peer Reviewed
• [Journal Article] Transcription factor GATA-3 is essential for lens development
  • Author(s): Maeda A, Moriguchi T*, Hamada M, Kusakabe M, Fujioka Y, Nakano T, Yoh K, Lim K-C, Engel JD, Takahashi S
  • Journal Title: Dev Dyn (in press)
  • Peer Reviewed
• [Journal Article] GATA1 and GATA2 function in hematopoietic differentiation
  • Author(s): Moriguchi T, Suzuki M, Engel JD and Yamamoto M
  • Journal Title: Hematopoietic Stem Cell Biology(The Human Press Inc) (in press)
  • Peer Reviewed
• [Presentation] Gata1 遺伝子発現制御領域の血球分化段階特異的な機能的貢献 (2009)
  • Author(s): 森口 尚
  • Organizer: 遺伝情報DECODE 湯沢ワークショップ
  • Place of Presentation: 新潟
  • Year and Date: 2009-01-19
• [Presentation] Gata1遺伝子発現制御領域の血球分化段階特異的な機能的貢献 (2009)
  • Author(s): MoriEuchi Suzuki M, Ohneda K and Yamamoto M.
  • Organizer: 遺伝情報DECODE冬のワークショップ
  • Place of Presentation: 湯沢
  • Year and Date: 2009-01-19
• [Presentation] Differential contribution of GATA1 hematopoietic enhancer to erythroid differentiation (2008)
  • Author(s): 森口 尚、鈴木未来子、山本雅之
  • Organizer: 第31回日本分子生物学会年会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-09
• [Presentation] Differential contribution of the Gatal gene hematopoietic enhancer to erythroid differentiation (2008)
  • Author(s): Moliguchi T, Suzuki M, Ohneda K and Yamamoto M.
  • Organizer: 第31回日本分子生物学会年会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-09
• [Presentation] Differential contribution of the Gatal gene hematopoietic enhancer to erythroid differentiation (2008)
  • Author(s): Morigichi T, Suzuki M, Ohneda K and Yamamoto M.
  • Organizer: 16^<th> Annual Hemoglobin Switching Conference
  • Place of Presentation: Moterey, California, USA
  • Year and Date: 2008-10-21
• [Presentation] GATA-1 hematopoietic enhancer confers its early erythroid progenitor-specific regulation (2008)
  • Author(s): Moriguchi T, Suzuki M and Yamamoto M
  • Organizer: 16th Annual Hemoglobin Switching Conference
  • Place of Presentation: モントレー、カリフォルニア
  • Year and Date: 2008-10-11
• [Presentation] Differential contribution of GATA1 hematopoietic enhancer to erythroid differentiation (2008)
  • Author(s): Moriguchi T, Suzuki M and Yamamoto M
  • Organizer: The 21^<st> Naito Conference
  • Place of Presentation: 山梨
  • Year and Date: 2008-06-24
• [Presentation] Differential contribution of the Gatal gene hematopoietic enhancer to erythroid differentiation (2008)
  • Author(s): Mori2uchi T, Suzuki M, Ohneda K and Yamamoto M.
  • Organizer: The 21^<st> Naito Conference
  • Place of Presentation: 山梨
  • Year and Date: 2008-06-24
• [Presentation] 大腸菌人工染色体を用いたGATA-1遺伝子の制御機構の解明 (2008)
  • Author(s): 森口 尚
  • Organizer: 08'遺伝情報DECODE冬のワークショップ
  • Place of Presentation: 湯沢
  • Year and Date: 2008-01-24
• [Presentation] Differential contribution of GATA1 hematopoietic enhancer to erythroid differentiation (2008)
  • Author(s): 森口 尚、鈴木未来子、山本雅之
  • Organizer: DECODE 湯沢ワークショップ
  • Place of Presentation: 新潟
  • Year and Date: 2008-01-21
• [Presentation] High affinity double GATA-binding site is indispensable for proper erythroid development (2007)
  • Author(s): Moriguchi T, Suzuki M and Yamamoto M
  • Organizer: The 2nd JST-ERATO symposium
  • Place of Presentation: つくば
  • Year and Date: 2007-12-21
• [Presentation] Gatal hematopoietic enhancer confers its early erythroid progenitor-specific regulation (oral presentation) (2007)
  • Author(s): Takashi Moriguchi
  • Organizer: National University of Singapore-Tohoku University/Centre of Excellence Joint Symposium
  • Place of Presentation: Singapore
  • Year and Date: 2007-10-24
• [Presentation] GATA-1 hematopoietic enhancer confers its early erythroid progenitor-specific regulation (2007)
  • Author(s): Moriguchi T, Suzuki M and Yamamoto M
  • Organizer: National University of Singapore-Tohoku University/Centre of Excellence Joint Symposium
  • Place of Presentation: シンガポール
  • Year and Date: 2007-09-05
• [Book] Hematopoietic Stem Cell Biology Chapter ; GATA1 and GATA2 function in hematopoietic differentiation (2009)
  • Author(s): Morieuchi T, Suzuki M, Engel JD. And Yammoto M.
  • Publisher: Human Press Inc.(印刷中)
• [Remarks]
  • URL: http://dmbc.med.tohoku.ac.jp/official/index.html
• [Remarks]
  • URL: http://dmbc.med.tohoku.ac.jp/official/index.html