1999 Fiscal Year Final Research Report Summary
Regulation and Function of Erythroid Transcription Factors.
| Project/Area Number |
09480183
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Molecular biology
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| Research Institution | University of Tsukuba |
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Principal Investigator |
YAMAMOTO Masayuki University of Tsukuba, Institute of Basic Medical Sciences, Professor., 基礎医学系, 教授 (50166823)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Satoru University of Tsukuba, Institute of Basic Medical Sciences, Lecturer., 基礎医学系, 講師 (50271896)
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| Project Period (FY) |
1997 – 1999
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| Keywords | transcription factor / GATA-1 / GATA-2 / NF-E2 / erythroid cells / differentiation / hematopoietic stem cells / genetargeting |
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| Research Abstract |
(1) Transcriptional regulation of transcription factors.
Transcriptional regulatory mechanisms of GATA-1, GATA-2 and mafK genes were analyzed. GATA-dependent enhancer was identified for erythroid- and megakaryocyte-specific expression of GATA-1 gene. Hematopoietic and cardiac expression of mafK gene was also found to be GATA-dependent. GATA-2 gene regulatory region, active in hematopoietic stem cells and developing neural tissues, was identified, and detailed analysis is now in progress.
(2) GATA-1 function in vivo
We generated transgenic mice bearing GATA-1, GATA-2 or GATA-3 cDNA driven by GATA-1 gene regulatory region. These mice were crossed with GATA-1 knock-down mice to test the function of each GATA factor in vivo environment where GATA-1 was reduced to 5%. To our surprise, GATA-2 and GATA-3 acted for GATA-1 in vivo, and the embryos with GATA-1 knock-down allele were rescued. Thus we concluded that GATA-1 generegulationis critical to the identity of GATA-1 function.
(3) Small Maf proteins for erythroid membraneintegrity.
mafK-null and mafG-null mice were crossed to generated compound mutant mice. These mice were anemic, and their red blood cells were markedly deformed. Analysis of erythrocyte membrane revealed the abnormal accumulation of yet unidentified proteins. This result shows the importance of small Maf proteins for red cell membraneintegrity.
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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 N-terminal Neh2 domain."Genes Dev.. 13. 76-86 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Kobayashi, A., Itoh, E., Toki, T., Takahashi, S-i, Igarashi, K., Hayashi, N. and Yamamoto, M.: "Molecular cloning and functional characterization of a new CNC family transcription factor Nrf3."J. Biol. Chem.. 274. 6443-6452 (1999)
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[Publications] Minegishi, N., Ohta, J., Yamagiwa, H., Suzuki, N., Kawauchi, S., Zhou, Y., Takahashi, S., Hayashi, N., Engel, J.D. and Yamamoto, M.: "The mouse GATA-2 gene is expressed in the aorta-gonads-mesonephros region."Blood. 93. 4196-4207 (1999)
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[Publications] Kawauchi, S., Takahashi, S., Nakajima, O., Ogino, H., Morita, M., Nishizawa, M., Yasuda, K. and Yamamoto, M.: "Regulation of lens fiber cell differentiation by transcription factor c-Maf."J. Biol. Chem.. 274. 19254-19260 (1999)
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[Publications] Onodera, K., Shavit, J.A., Motohashi, H., Katsuoka, F., Akasaka, J-e., Engel, J.D. and Yamamoto, M.: "Characterization of the murine mafF gene."J. Biol. Chem.. 274. 21162-21169 (1999)
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[Publications] Yoshida, C., Tokumasu, F., Hohmura, K.I., Bungert, J., Hayashi, N., Nagasawa, T., Engel, J.D., Yamamoto, M., Takeyasu, K. and Igarashi, K.: "Long range interaction of cis-DNA elements mediated by architectural transcription factor Bach1."Genes Cells. 4. 643-655 (1999)
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[Publications] Nakajima, O., Takahashi, S., Harigae, H., Furuyama, K., Hayashi, N., Sassa, S. and Yamamoto, M.: "Heme deficiency in erythroid lineage causes differentiation arrest and cytoplasmic iron overload."EMBO J.. 18. 6282-6289 (1999)
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[Publications] Nishimura, S., Takahashi, S., Kuroha, T., Suwabe, N., Nagasawa, T., Trainor, C. and Yamamoto, M.: "A GATA box in the GATA-1 gene hematopoietic enhancer is critical element in the network of GATA factors and sites that regulate this gene."Mol. Cell. Biol.. 20. 713-723 (2000)
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[Publications] Kobayashi, A., Yamagiwa, H., Hoshino, H., Muto, A., Sato, K., Morita, M., Hayashi, N., Yamamoto, M. and Igarashi, K.: "A combinatorial code for gene expression generated by transcription factor Bach2 and MAZR (MAZ-related factor) through BTB/POZ domain."Mol. Cell. Biol.. 20. 1733-1746 (2000)
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[Publications] Pan, X., Minegishi, N., Harigae, H., Yamagiwa, H., Minegishi, M., Akine, Y. and Yamamoto, M.: "Identification of human GATA-2 gene distal IS exon and its expression in hematopoietic stem cell fractions."J. Biochem.. 127. 105-112 (2000)
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