| Project/Area Number |
10670959
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Kumamoto University |
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Principal Investigator |
OIKE Yuichi (1999) School of Medicine, Kumamoto University, Associate Professor, 医学部, 助手
山口 祐司 (1998) 熊本大学, 医学部, 講師 (00220286)
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| Co-Investigator(Kenkyū-buntansha) |
尾池 雄一 熊本大学, 医学部, 助手
YAMAGUCHI Yuji School of Medicine, Kumamoto University, Assistant Professor (00220286)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1998: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | Eosinophil / MBP / GATA-1 / GATA-2 / C / EBP / Vasculo-angiogenesis / Gene trap / CBP |
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| Research Abstract |
Differentiation of eosinophils from myeloid progenitors is regulated by several different cytokines, including IL-3, GM-CSF and IL-5. However the molecular basis for the commitment of hematopoietic stem cells to the eosinophil lineage remains to be elucidated. We have been characterizing the regulatory regions of genes encoding eosinophil-specific proteins, including eosinophil peroxidase (EPO) Charcot-Leyden crystal (CLC) protein, and eosinophil major basic protein (MBP), to identify transcription factors involved in regulating the commitment and terminal differentiation of myeloid progenitors to the eosinophil lineage.
We demonstarted a major positive regulatory role for GATA-1 and a negative regulatory role for GATA-2 in MBP gene transcription. Further analysis of the MBP promoter region identified a C/EBP consensus binding site 6 bp upstream of the functional GATA-binding site in the MBP gene. In the eosinophilic cell line, HT93A, C/EBPα mRNA expression decreased significantly concomitant with eosinophilic differentiation,whereas C/EBPβ expression was markedly increased. We show that both C/EBPβand GATA-1 can bind simultaneously to the C/EBP- and GATA-1 binding sites in the MBP promoter and that synergistically transactivate the MBP P2 promoter with GATA-1. In addition, we provide evidence that FOG, a cofactor for GATA-binding proteins, may act as a negative cofactor in the eosinophil linegae, unlike its role as a positive cofactor for erythroid and megakaryocyte gene expression.
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