2016 Fiscal Year Final Research Report
Integrated elucidation of the transcriptional regulatory mechanisms of human ABO blood group gene using iPS cells
Project/Area Number |
26293161
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Partial Multi-year Fund |
Section | 一般 |
Research Field |
Legal medicine
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Research Institution | Gunma University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
高橋 遥一郎 群馬大学, 医学(系)研究科(研究院), 助教 (50640538)
佐野 利恵 群馬大学, 医学(系)研究科(研究院), 講師 (70455955)
中島 たみ子 群馬大学, 医学(系)研究科(研究院), 講師 (40008561)
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Project Period (FY) |
2014-04-01 – 2017-03-31
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Keywords | ABO式血液型 |
Outline of Final Research Achievements |
The human ABO blood group system is important in blood transfusion. However, the mechanisms regulating ABO gene expression remain obscure in epithelial cells. On the basis of DNase I-hypersensitive sites and histone modifications in and around ABO in epithelial cells, we prepared reporter plasmids including a putative enhancer downstream from ABO. Subsequent luciferase assays indicated a novel positive regulatory element (+22.6-kb site) in an epithelial cell-specific manner. Expression of ABO and B-antigen was reduced in gastric cancer KATOIII cells by biallelic deletion of the site using the CRISPR/Cas9 system. Electrophoretic mobility shift assay and chromatin immunoprecipitation assay demonstrated that the site bound to an epithelial cell-specific transcription factor Elf5. ELF5 knockdown with shRNA reduced both endogenous transcription from ABO and B-antigen expression in the cells. ABO expression seems to be dependent upon an enhancer bound by Elf5 in epithelial cells.
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Free Research Field |
法医学
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