| Project/Area Number |
10480163
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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 |
Functional biochemistry
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| Research Institution | Tohoku University |
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Principal Investigator |
HAYASHI Norio Tohoku University, Graduate School of Medicine, Professor (00004606)
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| Co-Investigator(Kenkyū-buntansha) |
IGARASHI Kazuhiko Hiroshima University, Faculty of Medicine, Professor (00250738)
KOBAYASHI Akira Tohoku University, Graduate School of Medicine, Assistant Professor (50292214)
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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 |
¥9,700,000 (Direct Cost: ¥9,700,000)
Fiscal Year 1999: ¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 1998: ¥5,800,000 (Direct Cost: ¥5,800,000)
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| Keywords | Heme / Transcription / Heme-oxygenase 1 / Bach1 / ヘム生合成調節 / ヘム調節モチーフ / 転写調節 / Nrf3 / ヘムオキシゲナーゼ / コプロポルフィリノーゲンオキシダーゼ / NF-E2 / MafK / 5-アミノレブリン酸合成酵素 |
|---|
| Research Abstract |
The purpose of this study is to understand the regulatory mechanisms of gene expression promoting erythroid cell differentiation. We examined the gene regulatory mechanisms of coproporphyrinogen (CPO) gene using reporter assays in cultured cells. The CPO gene is specifically active in erythroid cells but not in non-erythroid cells. We identified a novel motif CPRE, which appeared to be important for the differential expression of the gene. We also examined the function of Nrf3 and Bach1, which are members of the CNC transcription factor family. Among the members of this family, NF-E2 p45 is considered as a key transcription factor for erythroid differentiation. Molecular dissection of Nrf3 revealed a novel motif interacting with caspase 9. Biochemical analysis revealed that Bach1 associates with heme. Heme-bound Bach1 lost its DNA binding ability, suggesting that repressor activity of Bach1 is abrogated by heme. Consistently, Bach1-null mice displayed constitutive activation of heme-oxygenase 1 gene, which is a candidate target gene of Bach1. Thus, these data support the contention that Bach1 is a sensor of heme concentration and translates the heme abundance into the gene expression.
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