2006 Fiscal Year Final Research Report Summary
Analysis of cooperative expression of the genes encoding glycosyltransferases involved in the histo-blood group ABH antigens.
| Project/Area Number |
16390192
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Legal medicine
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| Research Institution | University of Toyama (2005-2006)
Toyama Medical and Pharmaceutical University (2004) |
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Principal Investigator |
TAKIZAWA Hisao University of Toyama, Graduate School of Medicine and Pharmaceutical Science for Research, Professor, 大学院医学薬学研究部, 教授 (90171579)
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| Co-Investigator(Kenkyū-buntansha) |
HATA Yukiko University of Toyama, Graduate School of Medicine and Pharmaceutical Science for Research, Teaching Associate, 大学院医学薬学研究部, 教務職員 (30311674)
KOMINATO Yoshihiko Gunma University, Graduate School of Medicine, Professor, 大学院医学系研究科, 教授 (30205512)
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| Project Period (FY) |
2004 – 2006
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| Keywords | human ABO gene / antisense RNA / N-box / bHLH factor / transcriptional regulation / FUT1 gene / FUT2 gene |
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| Research Abstract |
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.
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