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个盒子被bHLH家族的转录抑制子识别。由于α 1→2聚焦转移酶参与A抗原和B抗原的合成，ABO基因与编码α 1→2聚焦转移酶的FUT基因共表达。通过对人FUT基因上游区域核苷酸序列的检测，发现E box A类和B类位点结合bHLH家族转录激活因子，提示bHLH家族转录调节因子可能在这些基因的表达中起关键作用。由于转录bHLH抑制子可以与其他转录bHLH激活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并抑制转录，因此下调这些抑制子可能会减轻FUT基因启动子对转录的抑制。此外，下调与ABO启动子上游N盒结合的因子可能会减轻这种抑制，从而导致ABO基因的表达。因此，bHLH家族转录抑制子的减少可能在FUT和ABO基因的共同表达中起作用，导致参与a或B抗原合成的糖基转移酶协同表达。

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.