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GENETIC CONTROL OF HEMATOPOIETIC CELL DOFFERENTIATION

Research Project

Project/Area Number 09044255
Research Category

Grant-in-Aid for international Scientific Research

Allocation TypeSingle-year Grants
SectionJoint Research .
Research Field Molecular biology
Research InstitutionTohoku University (1998)
University of Tsukuba (1997)

Principal Investigator

IGARASHI Kazuhiko  TOHOKU UNIV.SCHOOL OF MEDICINE,ASSOCIATE PROFESSOR, 医学部, 助教授 (00250738)

Co-Investigator(Kenkyū-buntansha) PATIENT Roger  KING'S COLLEGE,LONDON,PROFESSOR, ランドール研究所, 教授
ENGEL J.Douglas  NORTHWESTERN UNIV.PROFESSOR, 教授
YAMAMOTO Masayuki  TSUKUBA UNIV.INSTITUTE OF BASIC MEDICAL SCIENCES,PROFESSOR, 基礎医学系, 教授 (50166823)
プーシエント ロジャー  キングスカレッジ, ランドール研究所, 教授
エンゲル ダグラス  ノースウェスタン大学, 生化学部門, 教授
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥5,700,000 (Direct Cost: ¥5,700,000)
Fiscal Year 1998: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1997: ¥2,800,000 (Direct Cost: ¥2,800,000)
KeywordsNF-E2 / GATA / Bach / KNOCKOUT MOUSE / 血液細胞 / 赤血球 / 転写因子 / 細胞分化
Research Abstract

Hematopoiesis is a good model system for analyzing regulation of cell differentiation. Using this system, we tried to identify transcription factors that regulate cell differentiation. We analyzed function of NF-E2 and related factors, and accumulated novel as well as unexpected results. These findings should lead to understanding of molecular and genetic regulation of hematopoiesis.
(1) To identify novel NF-E2-related transcription factors, we carried out further homology screening. As a result, we succeeded in identifying sixth member of the NF-E2-related factors which we named Nrf3. Its expression profile suggested that Nrf3 may regulate differentiation of hematopoietic cell differentiation. We are now carrying out gene disruption experiment using mice system, together with Prof.Engel.
(2) By making nrf2-knockout mice and analyzing its phenotypic changes, we revealed that Nrf2 is a key essentail regulator of phase II de-toxifying system expression.
(3) The BTB domain of Bach1 and Bach2 appears to be involved in regulation of chromatin structure. Using atomic force microscopy, we revealed that Bach1, and possible Bach2, function as a novel type of architectural transcription factor that mediate DNA loop formation. As such, Bach1 may be involved in regulation of the globin gene locus control region.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] Nagai, T: "Regulation of NF-E2 activity in erythroleukemia cell differentiation." Journal of Biological Chemistry. 273. 5358-5365 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Igarashi, K.: "Multivalent DNA Binding Complex Generated by small Maf and Bach1 as a Possible Biochemical Basis for β-globin Locus Control Region Complex." Journal of Biological Chemistry. 273. 11783-11790 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Muto, A.: "Identification of Bach2 as a B cell-specific partner for small Maf proteins that negatively regulate the immunoglobulin heavy chain gene 3'enhancer" EMBO Journal. 17. 5734-5743 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Itoh, K.: "Keapl represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain." Genes and Development. 13. 76-86 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kobayashi, A.: "Molecular cloning and functional characterization of a new Cap'n'collar family transcription factor Nrf3." Journal of Biological Chemistry. 274. 6443-6452 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nagai, T., Igarashi, K., Akasaka, J., Furuyama, K., Fujita, H., Hayashi, N., Yamamoto, M.and Sassa, S.: "Regulation of NF-E2 activity in erythroleukemia cell differentiation" J.Biol.Chem.273. 5358-5365 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Igarashi, K., Hoshino, H., Muto, A., Suwabe, N., Nishikawa, S., Nakauchi, H., and Yamamoto, M.: "Multivalent DNA Binding Complex Generated by Small Maf and Bach1 as a Possible Biochemical Basis for beta-globin Locus Control Region Complex." J.Biol.Chem.273. 11783-11790 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Muto, A., Hoshino, H., Madisen, L., Yanai, N., Obinata, M., Karasuyama, H., Hayashi, N., Nakauchi, H., Yamamoto, M., Groudine, M., and Igarashi, K.: "Identification of Bach2 as a B cell-specific partner for small Maf proteiins that negativery regulate the immunoglobulin heavy chain gene 3' enhancer" EMBO J.17. 5734-5743 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] ItoH,K., Wakabayashi, N., Katoh, Y., Ishii, T., Igarashi, K., Engel, J.D., and Yamamoto, M.: "Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain." Genes Dev.3. 76-86 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kobayashi, A., Ito, E., Toki, T., Kogame, K., Takahashi, S., Igarashi, K., Hayashi, N., and Yamamoto, M.: "Molecular cloning and functional characterization of a new Cap'n'collar family transcription factor Nrf3." J.Biol.Chem.274. 6443-6452 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nagai,T.: "Regulation of NF-E2 activity in erythroleukemia cell differentiation." Journal of Biological Chemistry. 273. 5358-5365 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Igarashi,K.: "Multivalent DNA Binding Complex Generated by Small Maf and Bach1 as a Possible Biochemical Basis for β-globin Locus Control Region Complex." Journal of Biological Chemistry. 273. 11783-11790 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Muto,A.: "Identification of Bach2 as a B cell-specific partner for small Maf proteins that negatively regulate the immunoglobulin heavy chain gene 3' enhancer" EMBO Journal. 17. 5734-5743 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Itoh,K.: "Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain." Genes and Development. 13. 76-86 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kobayashi,A.: "Molecular cloning and functional characterization of a new Cap'n'collar family transcription factor Nrf3." Journal of Biological Chemistry. 274. 6443-6452 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] M tohashi, H. et al: "The World According to Maf" Nucleic Acids Res. 25. 2953-2959 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Itoh, K. et al: "An Nrf2/Small Maf Heterodimer Mediates the Induction of Phase II Detoxifying Enzyme Genes through Antioxidant Response Elements" Biochemical and Biophys. Res. Commun.236. 313-322 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Nagai, T. wt al.: "Regulation of NF-E2 Activity in Erythroleukemia Cell Differentiation" J. Biol. Chem.273 (in press). (1998)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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