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Analysis of cooperative expression of the genes encoding glycosyltransferases involved in the histo-blood group ABH antigens.

参与组织血型 ABH 抗原的糖基转移酶编码基因的协同表达分析。

基本信息

批准号：
16390192
负责人：
TAKIZAWA Hisao
金额：
$ 6.78万
依托单位：
University of Toyama (2005-2006)Toyama Medical and Pharmaceutical University (2004)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2006
项目状态：
已结题

项目摘要

Synthesis of the histo-blood group ABH antigens requires several glycosyltransferases. The A/B antigens are terminal carbohydrates synthesized by the sequential addition of sugers catalyzed by specific glycosyltransferases. These transferases require α(1,2) fucose modification of the precursor oligonucleotides, and thus A and B antigens can only be synthesized from H antigen. The molecular basis of control of the glycosyltransferase genes is of importance in obtaining a deeper understanding of the regulation and tissue specific expression of the products of those genes.In this study, we demonstrated the expression of antisense transcripts, complementary to the genomic DNA coding strand for the ABO gene encoding ABO glycosyltransferase. Naturally occurring antisense transcriptions have been reported to regulate gene expression through a variety of biological mechanisms. Therefore, the antisense transcript might be involved in the regulation of the ABO gene expression. Further studies will be needed to investigate the presence of antisense RNA to the FUT1 and FUT2 genes encoding α(1,2) fucosytransferase as well as the ABO gene.Moreover, we have confirmed that the ABO gene expression is negatively regulated by N-box upstream of the promoter and that the N box binds with a nuclear factor termed RACP. N-box is recognized by members of bHLH factor. The bHLH family of transcriptional regulators plays crucial roles in the development of various organs and cell types. Previously, we demonstrated that the ABO gene was co-expressed with the FUT1 and FUT2 genes. Inspection of the nucleotide sequences of the upstream region of the FUT1 and FUT2 genes revealed putative binding site of bHLH proteins, suggesting that the bHLH factors could play crucial roles in expression of the genes. Therefore, the N-box binding protein including to the RACP might mediate regulation for cooperative expression of those genes encoding glycosyltransferases involved in the ABH antigens.

组织血型ABH抗原的合成需要几种糖基转移酶。A/B抗原是由特异性糖基转移酶催化的糖的顺序加成合成的末端碳水化合物。这些转移酶需要前体寡核苷酸的α（1，2）岩藻糖修饰，因此A和B抗原只能由H抗原合成。糖基转移酶基因调控的分子基础对于深入理解这些基因产物的调控和组织特异性表达具有重要意义，在本研究中，我们证明了与编码ABO糖基转移酶的ABO基因的基因组DNA编码链互补的反义转录物的表达。据报道，天然存在的反义转录因子通过多种生物学机制调节基因表达。因此，反义转录本可能参与了ABO基因表达的调控。进一步的研究表明，ABO基因的表达受启动子上游N-box的负调控，且N-box与核因子RACP结合。N-box是bHLH因子的成员。bHLH家族的转录调节因子在各种器官和细胞类型的发育中起着至关重要的作用。以前，我们证明了ABO基因与FUT 1和FUT 2基因共表达。对FUT 1和FUT 2基因上游区核苷酸序列的分析显示bHLH蛋白的结合位点，提示bHLH因子在基因表达中起重要作用。因此，包括RACP在内的N盒结合蛋白可能介导编码ABH抗原中涉及的糖基转移酶的基因的协同表达的调节。