1998 Fiscal Year Final Research Report Summary
GENETIC CONTROL OF HEMATOPOIETIC CELL DOFFERENTIATION
| Project/Area Number |
09044255
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research . |
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| Research Field |
Molecular biology
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| Research Institution | Tohoku University (1998)
University of Tsukuba (1997) |
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Principal Investigator |
IGARASHI Kazuhiko TOHOKU UNIV.SCHOOL OF MEDICINE,ASSOCIATE PROFESSOR, 医学部, 助教授 (00250738)
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| 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)
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| Project Period (FY) |
1997 – 1998
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| Keywords | NF-E2 / GATA / Bach / KNOCKOUT MOUSE |
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| 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.
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[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)
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[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)
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[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)
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[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)
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[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)
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「研究成果報告書概要(欧文)」より
