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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| 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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Report
(4 results)
Research Products
(64 results)
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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
Related Report
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
Related Report
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
Related Report
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
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Peer Reviewed
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[Journal Article] Identification of the brackish water clam Corbicula japonica (Japanese name, Yamato-shijimi) and pecification of the growing district by PCR-based analysis of mitochondrial DNA2011
Author(s)
Fujihara, J, Yasuda, T, Ueki M, Fujita Y, Nakamura M, Oshiumi C, Hosozawa T, Nabika T, Harada Y, Kobayashi T, Nakajima T, Takeshita H
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Journal Title
Environmental Forensics Journal
Volume: 9
Issue: 2
Pages: 25-31
DOI
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Peer Reviewed
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[Journal Article] A case of fatal drug intoxication showing a high-density duodenal content by postmortem computed tomography.?2011
Author(s)
Sano R, Takahashi K, Kominato Y, Araki T, Yamamoto K, Takei H, Otake H, Awata S, Akuzawa H, Tago Y, Aoki H
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Journal Title
Leg Med (Tokyo).
Volume: 13
Pages: 39-40
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[Journal Article] 低酸素による核酸分解酵素DNASEI遺伝子の転写調節2010
Author(s)
佐野利恵, 中島たみ子, 小湊慶彦, 加藤恵理子, 高士祐一, 新田みなみ, 山根庸弘, 藤原純子, 竹下治男, 植木美鈴, 安田年博
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Journal Title
DNA多型
Volume: 18
Pages: 278-282
Related Report
Peer Reviewed
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[Journal Article] Expression of ABO blood-group genes is dependent upon an erythroid cell-specific regulatory element, which is deleted in individuals with the Bm phenotype
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, Uchikawa M
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