| Project/Area Number |
22390140
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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 |
Legal medicine
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| Research Institution | Gunma University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
NAKAJIMA Tamiko 群馬大学, 大学院・医学系研究科, 助教 (40008561)
SANO Rie 群馬大学, 大学院・医学系研究科, 助教 (70455955)
ASAO Takayuki 群馬大学, 大学院・医学系研究科, 准教授 (40212469)
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| Project Period (FY) |
2010 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥16,510,000 (Direct Cost: ¥12,700,000、Indirect Cost: ¥3,810,000)
Fiscal Year 2012: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2011: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2010: ¥10,010,000 (Direct Cost: ¥7,700,000、Indirect Cost: ¥2,310,000)
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| Keywords | ABO 式血液型 / 転写調節領域 / 亜型 / Bm 型 / 輸血 / ABO式血液型遺伝子 / エンハンサー / レポーターアッセイ / ヒストンデアセチラーゼ |
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| Research Abstract |
The ABO blood group is of great importance in blood transfusion and personal identification. However, the mechanisms regulating human ABO gene expression remain obscure. On the basis of DNase I hypersensitive sites in and upstream of ABO in the human erythroleukemia cell line K562 in publicly available expression data from the UCSC Genome Browser (http://genome.ucsc.edu), we prepared reporter plasmid constructs including these sites. Subsequent luciferase assays indicated a novel positive regulatory element in intron 1. This element was shown to enhance ABO promoter activity in an erythroid cell-specific manner. Electrophoretic mobility shift assays demonstrated that it bound to the tissue-restricted transcription factor GATA-1 and GATA-2. Mutation of the GATA motifs to abrogate binding of this factor reduced the regulatory activity of the element. Thus, GATA transcription factors seem to be involved in the cell-specific activity of the element. Furthermore, we found that Bm phenotypes were associated with a partial deletion in intron 1 involving the element as well as a single point mutation of GATA site leading to reduced activity of the element. Therefore, it is plausible that deletion or a single point mutation of the erythroid cell-specific regulatory element could down-regulate transcription in the B^m allele, leading to reduction of B antigen expression in cells of erythroid lineage, but not in mucus-secreting cells. These results support the contention that the enhancer-like element in intron 1 of ABO has a significant function in erythroid cells.
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