| 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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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥13,000,000 (Direct Cost: ¥13,000,000)
Fiscal Year 1999: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1998: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1997: ¥7,300,000 (Direct Cost: ¥7,300,000)
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| Keywords | transcription factor / GATA-1 / GATA-2 / NF-E2 / erythroid cells / differentiation / hematopoietic stem cells / genetargeting / NF-E2 / 造血幹細胞 / 遺伝子部分破壊マウス / 血球細胞分化 / GATA転写因子群 / CNC転写因子群 / 遺伝子破壊 / プロモーター破壊 / 蛋白質間相互作用 / 転写因子ネットワーク |
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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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