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

ABO血型系统生物科学进展-法医学的开创性工作-

• 批准号: 13307018
• 负责人: TAKIZAWA Hisao
• 金额: $ 18.47万
• 依托单位: TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13307018/
• 关键词: Blood groups; ABO blood group genes; ABO glycosyltransferases; Fucosyltransferases; Transcription; CpG islands; E box; N box; ABO式血液型; 遺伝子発現; 転写制御; DNAメチレーション; 転写抑制因子; FUT-2遺伝子; H遺伝子; 転写開始点; プロモーター; 5'RACE法; DNAメチル化

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.

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bHLH家族的转录抑制因子识别。由于α 1→2岩藻糖基转移酶参与A和B抗原的合成，因此ABO基因与编码α 1→2岩藻糖基转移酶的FUT基因共表达。对人FUT基因上游区的核苷酸序列的检查揭示了结合bHLH家族转录激活因子的E盒A类和B类位点，表明bHLH家族转录调节因子在这些基因的表达中可能起关键作用。由于转录bHLH阻遏物可以与其他转录bHLH激活物形成非功能性异源二聚体，从而抑制功能性异源二聚体的形成并抑制转录，因此阻遏物的下调可能会缓解FUT基因启动子对转录的抑制。此外，与ABO启动子上游的N盒结合的因子的下调可以解除抑制，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，这导致参与A或B抗原合成的糖基转移酶的协同表达。

项目成果

Koda Y, Soejima M, Kimura H: "The polymorphisms of fucosyltransferases.(Review)."Legal Med. 3. 2-14 (2001)

Koda Y、Soejima M、Kimura H：“岩藻糖基转移酶的多态性。（评论）。”法律医学。

Yamamoto, M, Luong TT, Williams T, Kominato Y, et al.: "Expression profiling of 68 glycosyltransferase genes in 27 different human tissues, by the Systematic Multiplex RT-PCR (SMRT-PCR) method, revealed clustering of sexually related tissues in hierarchic

Yamamoto, M、Luong TT、Williams T、Kominato Y 等人：“通过系统多重 RT-PCR (SMRT-PCR) 方法对 27 个不同人体组织中的 68 个糖基转移酶基因进行表达谱分析，揭示了性相关组织的聚类

Koda Y, Ishida T, Tachida H, et al.: "DNA sequence variation of the human ABO-secretor locus (FUT2) in New Guinean populations : possible early human migration from Africa."Hum Genet. 113. 534-541 (2003)

Koda Y、Ishida T、Tachida H 等人：“新几内亚人群中人类 ABO 分泌基因座 (FUT2) 的 DNA 序列变异：可能是早期人类从非洲迁徙。”Hum Genet。

Koda Y, Tachida H, Pang H, Liu Y, Soejima M, Ghaderi AA, Takenaka O, Kimura H: "Contrasting patterns of polymorphisms at ABO-Secretor gene(FUT2) and plasma α(1,3)fucosyltransferase gene(FUT6) in human populations."Genetics. 158. 747-756 (2001)

Koda Y、Tachida H、Pang H、Liu Y、Soejima M、Ghaderi AA、Takenaka O、Kimura H：“ABO 分泌基因 (FUT2) 和血浆 α(1,3) 岩藻糖基转移酶基因 (FUT6) 多态性的对比模式在人群中。“遗传学。158. 747-756 (2001)

Tamai O, Koda Y, Sccjima M, Kimura H, et al.: "Caveolae in mesangial cells and caveolin expression in mesangial proliferative glomerulonephritis."Kidney Int. 59. 471-480 (2001)

Tamai O、Koda Y、Sccji​​ma M、Kimura H 等人：“系膜细胞中的小窝和小窝蛋白在系膜增生性肾小球肾炎中的表达。”Kidney Int。