| Budget Amount *help |
¥13,390,000 (Direct Cost: ¥10,300,000、Indirect Cost: ¥3,090,000)
Fiscal Year 2016: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2015: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2014: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
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| 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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