Transcriptional regulation of the human ABO histo-blood group genes is dependent on the negative regulation through the N box upstream of the proximal promoter

人类 ABO 组织血型基因的转录调控依赖于近端启动子上游 N 盒的负调控

• 批准号: 15590575
• 负责人: KOMINATO Yoshihiko
• 金额: $ 1.86万
• 依托单位: Gunma University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590575/
• 关键词: ABO gene; transcription; N box; repression; promoter; ABO遺伝子

Our previous studies of the transcriptional regulatory mechanism of the human ABO gene indicated that negative regulatory elements are present in the sequence upstream of the proximal promoter, suggesting that transcription from the ABO proximal promoter is in part controlled by silencer elements just upstream of the promoter. In this study, we have confirmed that ABO gene expression is negatively regulated by the sequence upstream of the proximal promoter in KATOIII cells, and that the region between -202 and -118 is involved in the negative regulation in cells of both epithelial and erythroid lineages. Transient transfection experiments in KATOIII cells using a luciferase reporter plasmid carrying mutated N box at -196 to -191 demonstrated that the N box is a negative regulatory element in the -202 to -118 sequence. Using electrophoretic mobility shift assay, we showed that the N box binds with a nuclear factor, termed RACP, derived from KATOIII cells. These results suggest that repression of transcription from the ABO proximal promoter is partially dependent upon the N box, and that down-regulation of RACP may relieve the repression, thereby leading to expression of the ABO gene during maturation of cells in the epithelial lineage as well as the erythroid lineage.

我们以前的人类ABO基因的转录调控机制的研究表明，负调控元件存在于序列上游的近端启动子，这表明从ABO近端启动子的转录部分是由沉默元件上游的启动子控制。在这项研究中，我们已经证实，ABO基因的表达是负调控的KATOIII细胞中的近端启动子的上游序列，并在-202和-118之间的区域是在上皮细胞和红系细胞的负调控。在KATOIII细胞中使用携带-196至-191处突变的N盒的荧光素酶报告质粒的瞬时转染实验证明，N盒是-202至-118序列中的负调控元件。使用电泳迁移率变动分析，我们表明，N盒结合的核因子，称为RACP，来自KATOIII细胞。这些结果表明，从ABO近端启动子转录的抑制部分依赖于N盒，RACP的下调可能会缓解抑制，从而导致在上皮细胞系以及红系细胞成熟过程中ABO基因的表达。

项目成果

Yamamoto M, Yamamoto F, Luong TT, Williams T, Kominato Y, Yamamoto F: "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 tissue

Yamamoto M、Yamamoto F、Luong TT、Williams T、Kominato Y、Yamamoto F：“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，揭示了性相关的聚类

Transcription starting from an alternative promoter leads to the expression of the human ABO histo-blood group antigen

• DOI: 10.1046/j.1537-2995.2003.00382.x
• 发表时间: 2003-05-01
• 期刊: TRANSFUSION
• 影响因子: 2.9
• 作者: Hata, Y;Kominato, Y;Yamamoto, F
• 通讯作者: Yamamoto, F

A novel 56-bp variable tandem repeat polymorphism in the human deoxyribonuclease I gene and its population data.

• DOI: 10.1016/j.legalmed.2004.07.001
• 发表时间: 2004-10-01
• 期刊: Legal medicine (Tokyo, Japan)
• 作者: Yasuda, Toshihiro;Iida, Reiko;Kishi, Koichiro
• 通讯作者: Kishi, Koichiro

Transcriptional regulation of the human ABO histo-blood group genes is dependent on the N box upstream of the proximal promoter

• DOI: 10.1111/j.0041-1132.2004.04028.x
• 发表时间: 2004-12-01
• 期刊: TRANSFUSION
• 影响因子: 2.9
• 作者: Kominato, Y;Hata, Y;Kishi, K
• 通讯作者: Kishi, K

Molecular evolution of shark and other vertebrate DNases I

鲨鱼和其他脊椎动物 DNA 酶 I 的分子进化

• 发表时间: 2004
• 期刊: European Journal of Biochemistry 271・22
• 作者: Kakinoki K;Fujino Y;Suzuki Y;Li S;Tanioka Y;Sakai T;Kuroda Y;Cesar F.Ortega-Cava;Masanori Abe;Komine M;Toshihiro Yasuda
• 通讯作者: Toshihiro Yasuda