Differential activity of interferon-α8 promoter is regulated by Oct-1 and a SNP that dictates prognosis of glioma.
Differential activity of interferon-α8 promoter is regulated by Oct-1 and a SNP that dictates prognosis of glioma.
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DOI：
10.4161/onci.19964
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发表时间：
2012-07-01
期刊：
影响因子：
7.2
通讯作者：
Okada H
中科院分区：
文献类型：
--
作者：
Kohanbash G;Ishikawa E;Fujita M;Ikeura M;McKaveney K;Zhu J;Sakaki M;Sarkar SN;Okada H
我们以前曾报道过IFNA 8的单核苷酸多态性（SNP）rs 12553612与AA基因型胶质瘤患者的总生存率比AC基因型患者更好相关。由于rs 12553612位于IFNA 8启动子中，我们假设A等位基因与C等位基因相比允许增强的IFNA 8启动子活性。在人单核细胞衍生的THP-1细胞系中的报告基因测定证明了与C-等位基因相比，A-等位基因的上级启动子活性。电泳迁移率变动分析（EMSA）进一步表明，A-基因型特异性结合更多的核蛋白比C-基因型，包括转录因子Oct-1。此外，编码Oct-1和报告构建体的质粒的共转染揭示了Oct-1增强了A-而不是C-等位基因的启动子活性。综上所述，我们的数据表明，rs 12553612 SNP中的A等位基因，这与更好的胶质瘤患者的生存率相关，允许IFNA 8通过允许Oct-1结合而转录，这在具有C等位基因的患者中是不存在的，并表明IFNA 8介导的胶质瘤进展的免疫监视的分子机制。
We have previously reported that the single nucleotide polymorphism (SNP) rs12553612 in IFNA8 is associated with better overall survival of glioma patients with the AA-genotype compared with patients with the AC-genotype. As rs12553612 is located in the IFNA8 promoter, we hypothesized that the A-allele allows for an enhanced IFNA8 promoter activity compared with the C-allele. Reporter assays in the human monocyte derived THP-1 cell line demonstrated a superior promoter activity of the A-allele compared with the C-allele. Electrophoretic mobility shift assays (EMSA) further demonstrated that the A-genotype specifically binds to more nuclear proteins than the C-genotype, including the transcription factor Oct-1. Further, co-transfection of plasmids encoding Oct-1 and the reporter constructs revealed that Oct-1 enhanced the promoter activity with the A- but not the C-allele. Taken together, our data demonstrate that the A-allele in the rs12553612 SNP, which is associated with better glioma patient survival, allows for IFNA8 transcription by allowing for Oct-1 binding, which is absent in patients with C allele, and suggests a molecular mechanism of IFNA8 mediated immune-surveillance of glioma progression.
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DOI：
10.1084/jem.20101159
发表时间：
2011-09-26
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Fuertes MB;Kacha AK;Kline J;Woo SR;Kranz DM;Murphy KM;Gajewski TF
通讯作者：
Gajewski TF
影响因子：
3.8
作者：
Schwartzbaum, Judith A.;Ahlbom, Anders;Feychting, Maria
通讯作者：
Feychting, Maria
影响因子：
5.5
作者：
Dhiman, Neelam;Ovsyannikova, Inna G.;Poland, Gregory A.
通讯作者：
Poland, Gregory A.
影响因子：
14.9
作者：
Heinemeyer, T;Wingender, E;Kolchanov, NA
通讯作者：
Kolchanov, NA
DOI：
10.1084/jem.20101158
发表时间：
2011-09-26
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Diamond MS;Kinder M;Matsushita H;Mashayekhi M;Dunn GP;Archambault JM;Lee H;Arthur CD;White JM;Kalinke U;Murphy KM;Schreiber RD
通讯作者：
Schreiber RD