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

Transcriptional regulation of the human ABO histo-blood group genes is dependent on the N box upstream of the proximal promoter
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DOI:
10.1111/j.0041-1132.2004.04028.x
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发表时间:
2004-12-01
期刊:
影响因子:
2.9
通讯作者:
Kishi, K
Kishi, K
中科院分区:
医学3区
文献类型:
--
作者:
Kominato, Y;Hata, Y;Kishi, K

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背景技术背景:我们以前的人类ABO基因的转录调控的研究表明,负调控元件存在于序列的上游,从近端启动子。研究设计和方法:用携带ABO上游序列的荧光素酶报告质粒进行瞬时转染实验,并用从人胃癌KATO Ⅲ细胞制备的核提取物进行电泳迁移率变动分析。结果表明,-202 ~-118区域参与ABO基因转录的负调控。在KATOIII细胞中,用携带-196至-191处突变的N盒的报告质粒进行瞬时转染实验,证明N盒是-202至-118序列中的负调控元件。电泳迁移率变动分析表明,N盒与核因子从KATOIII cells.CONCLUSION:这些结果表明,从ABO近端启动子的转录抑制部分依赖于N盒。因此,蛋白质与N盒的结合减少可能在ABO基因表达中起直接作用。
BACKGROUND: Our previous studies of the transcriptional regulation of the human ABO gene indicated that negative regulatory elements are present in the sequence just upstream from the proximal promoter. The role of the-275 to-118 region in regulation of ABO gene transcription is further characterized.STUDY DESIGN AND METHODS: Transient transfection experiments into various cells were performed with luciferase reporter plasmids carrying ABO upstream sequences, and electrophoretic mobility shift assay was carried out with a nuclear extract prepared from the human gastric cancer KATOIII cells.RESULTS: It is shown that the -202 to -118 region is involved in the negative regulation of ABO gene transcription in all cell lines examined. Transient transfection experiments in KATOIII cells with a reporter plasmid carrying mutated N box at -196 to -191 demonstrate that the N box is a negative regulatory element in the -202 to -118 sequence. Electrophoretic mobility shift assays indicate that the N box binds with a nuclear factor from KATOIII cells.CONCLUSION: These results indicate that repression of transcription from the ABO proximal promoter is partially dependent upon the N box. Therefore, reduced binding of the protein with the N box might play a direct role in ABO gene expression.