2012 Fiscal Year Final Research Report
Elucidation of ABO blood group gene expression though chromatin remodeling
| 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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| Keywords | ABO 式血液型 / 転写調節領域 / 亜型 / Bm 型 / 輸血 |
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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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[Journal Article] Expression of ABO blood-group genes is dependent upon an erythroid cell-specific regulatory element that is deleted in persons with the Bmphenotype2012
Author(s)
Sano R, Nakajima T, Takahashi K, Kubo R, Kominato Y, Tsukada J, Takeshita H, Yasuda T, Ito K, Maruhashi T, Yokohama A, Isa K, Ogasawara K and Uchikawa M
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Journal Title
Blood
Volume: 119
Pages: 5301-5310
Peer Reviewed
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[Journal Article] Genetic and expression analysis of SNPs in the human deoxyribonuclease II: SNPs in the promoter region reduce its in vivo activity through decreased promoteractivity2012
Author(s)
Kimura-Kataoka K, Yasuda T, Fujihara J, Toga T, Ono R, Otsuka Y, Ueki M, Iida R, Sano R, Nakajima T, Kominato Y, Kato H and Takeshita H
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Journal Title
Electrophoresis
Volume: 33
Pages: 2852-2858
Peer Reviewed
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[Journal Article] Genetic variation of FUT2 in a Vietnamese population: identification of two novel Se enzyme-inactivatingmutations2012
Author(s)
Soejima M, Fujimoto R, Agusa T, Iwata H, Fujihara J, Takeshita H, Minh TB, Trang PT, Viet PH, Nakajima T, Yoshimoto J, Tanabe S and Koda Y
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Journal Title
Transfusion
Volume: 52
Pages: 1268-1275
Peer Reviewed
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[Journal Article] Nonsynonymous single-nucleotide polymorphisms of the human apoptosis-related endonuclease--DNA fragmentation factor beta polypeptide, endonuclease G, and Flap endonuclease-1--genes show a low degree of geneticheterogeneity2012
Author(s)
Takeshita H, Fujihara J, Ueki M, Iida R, Koda Y, Soejima M, Yuasa I, Kato H, Nakajima T, Kominato Y and Yasuda T
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Journal Title
DNA Cell Biol
Volume: 31
Pages: 36-42
Peer Reviewed
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