The differential expression of blood group P1-and P2-A4GALT alleles is stimulated by transcription factor EGR1

• Main Authors: Yi-Jui Tsai, 蔡易叡
• Other Authors: 余榮熾
• Format: Others
• Language: zh-TW
• Published: 2017
• Online Access: http://ndltd.ncl.edu.tw/handle/4rdrvp

碩士 === 國立臺灣大學 === 生化科學研究所 === 105 === The P1/P2 phenotypic polymorphism is one of the earliest blood groups discovered in humans. These blood groups have been connected to presence of different levels of expression of the A4GALT gene in P1 and P2 red cells; however, the detailed molecular genetic mechanism that leads to these two phenotypes has not been established. Following our previous identification of an association between the SNPs rs2143918 and rs5751348 in A4GALT gene and the P1/P2 phenotype, we conduct a survey of transcription factors that might connect these SNPs with the differential expression of the P1-A4GALT and P2-A4GALT alleles. An in silico analysis of potential transcription factor binding motifs within the polymorphic rs2143918 and rs5751348 genomic regions was performed, and this was followed by reporter assays examining the candidate transcription factors, gene expression profiling, electrophoretic mobility shift assays, and P1-A4GALT and P2-A4GALT allelic expression analysis. The results revealed that the differential binding of transcription factor EGR1 to the polymorphic SNP rs5751348 genomic region leads to differential activation of P1-A4GALT and P2-A4GALT expression and this consequently results in the quantitative difference of P1 antigen expression levels in P1 and P2 red cells. The present investigation has elucidated the molecular genetic details associated with the P1/P2 blood groups and revealing the first human blood group whose formation involves the transcriptional activity of a specific transcription factor and its interaction with genetic polymorphism within the gene regulatory region.