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Promoter analysis of the interferon regulatory factor 2 and the SNP analysis of the gene

干扰素调节因子2启动子分析及基因SNP分析

基本信息

批准号：
15591187
负责人：
FUKAI Kazuyoshi
金额：
$ 2.24万
依托单位：
Osaka City University Graduate School of Medicine
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-15591187/
关键词：
IRF2 polymorphism promoter psoriasis 多因子遺伝遺伝子多型転写因子 USF

项目摘要

Interferon regulatory factor 2 (IRF-2) is a transcriptional regulatory protein which represses the expression of interferon-alpha/beta genes. In mice lacking IRF-2, the inflammatory skin disease very similar to human psoriasis develops spontaneously. In addition, IRF-2 gene is located at human chromosome 4q35, where a familial psoriasis susceptibility locus has been mapped. Therefore, we hypothesized the IRF-2 gene is a possible candidate gene for psoriasis.Genotyping of -535G>A was performed by NlaIII-restriction flagment polymorphism (RFLP). Gel-shift and super-shift analysis were employed for the accessment of the binding abilities of transcription factors. To demonstrate differential transcriptional activities, luciferase reporter assays were perforemed.We identified a -535G>A polymorphism in the IRF-2 transcriptional promoter. The -535A allele was more frequent (p= 0.035) in early-onset (less than 41 years of age) psoriasis in Japan, although this was not associated with the old-onset (41 years or older) psoriasis. The -535G allele was found to bind upstream stimulatory factor (USF) by the supershift analysis, whereas the -535A allele did not bind USF. However, the reporter assay revealed no statistical difference of the transcriptional activity between -535A allele and -535G allele. Furthermore, co-transfection of the USF-1 expression vector did not stimulate the promoter activity of our luciferase reporter system.

干扰素调节因子2（Interferon Regulatory Factor 2，IRF-2）是一种抑制干扰素α/β基因表达的转录调节蛋白。在缺乏IRF-2的小鼠中，与人类银屑病非常相似的炎性皮肤病自发发展。此外，IRF-2基因定位于人类染色体4 q35，在那里一个家族性银屑病易感基因已被定位。因此，我们假设IRF-2基因可能是银屑病的候选基因。凝胶位移和超位移分析评价转录因子的结合能力。为了证明不同的转录活性，我们进行了荧光素酶报告基因分析，在IRF-2转录启动子中发现了一个-535G>A多态性。在日本，-535A等位基因在早发性（小于41岁）银屑病中更常见（p= 0.035），尽管这与老年性（41岁或以上）银屑病无关。超移位分析发现-535G等位基因与上游刺激因子（USF）结合，而-535A等位基因不与USF结合。报告基因检测结果显示，-535A和-535G等位基因的转录活性无统计学差异。此外，USF-1表达载体的共转染没有刺激我们的荧光素酶报告系统的启动子活性。