Progress in the biological science of ABO blood group system -a pioneer work in legal medicine-

我们对人类ABO基因转录调控机制的研究表明，ABO基因的转录受近端启动子上游的N盒调控。N盒被转录抑制因子bHLH家族识别。由于α-1-→-2岩藻糖基转移酶参与A和B抗原的合成，因此该基因与编码α-1-→-2岩藻糖基转移酶的FUT基因共表达。对人类FUT基因上游区核苷酸序列的检测发现，E盒A类和B类位点与bHLH家族的转录激活因子结合，表明bHLH家族的转录调控因子可能在这些基因的表达中发挥关键作用。由于转录水平的bHLH抑制因子可以与其他转录因子形成非功能性异二聚体，从而抑制功能性异二聚体的形成，从而抑制转录，因此下调抑制因子可能会缓解FUT基因启动子对转录的抑制作用。此外，下调与ABO启动子上游N盒结合的因子可能会解除抑制，从而导致ABO基因的表达。因此，bHLH家族转录抑制因子的减少可能在FUT和ABO基因的共表达中起作用，从而导致参与A或B抗原合成的糖基转移酶的协同表达。

Our studies of the transcriptional regulatory mechanism of the human ABO gene indicated that transcription of the ABO gene is regulated by the N box upstream the proximal promoter. N boxes are recognized by bHLH family of transcriptional repressers. Since α 1→2 fucosyltransferases are involved in the synthesis of A and B antigens, the ABO gene is co-expressed with the FUT genes encoding α 1→2 fucosyltransferases. Inspection of the nucleotide sequences of the upstream regions of the human FUT genes revealed E box class A and class B sites which bind bHLH family of transcriptional activators, suggesting that the bHLH family of transcriptional regulators could play crucial roles in expression of those genes. Since transcriptional bHLH repressers can form non-functional heterodimers with other transcriptional bHLH activators, thereby inhibiting the formation of functional heterodimers and repressing transcription, down-regulation of the repressers might relieve the repression of transcription from promoters of the FUT genes. Furthermore, down-regulation of a factor binding with the N box upstream the ABO promoter may relieve the repression, thereby leading to expression of the ABO gene. Therefore, reduction of bHLH family transcription represser may play a role in the co-expression of the FUT and ABO gene which leads to cooperative expression of glycosyltransferases involved in synthesis of A or B antigens.