Integrated elucidation of the transcriptional regulatory mechanisms of human ABO blood group gene using iPS cells

2016 Fiscal Year Final Research Report

• Project/Area Number: 26293161
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Legal medicine
• Research Institution: Gunma University
• Principal Investigator: Kominato Yosihhiko 群馬大学, 医学(系)研究科(研究院), 教授 (30205512)
• 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)
• Project Period (FY): 2014-04-01 – 2017-03-31
• 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.

Free Research Field

法医学