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首页> 外文期刊>Annals of Human Genetics >A Novel Polymorphic AP-1 Binding Element of the GFAP Promoter is Associated with Different Allelic Transcriptional Activities
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A Novel Polymorphic AP-1 Binding Element of the GFAP Promoter is Associated with Different Allelic Transcriptional Activities

机译：GFAP启动子的新型多态AP-1绑定元素与不同的等位基因转录活性相关联。

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SummaryThe Glial Fibrillary Acidic Protein (GFAP) gene encodes a cytoskeletal protein belonging to the intermediate filament family whose expression is considered as a marker of astrocytes differentiation. GFAP expression, shown to be upregulated as a consequence of brain gliosis, depends on hormones, growth factors, cytokine, and transcription factors and, among these latters, activator protein 1 (AP-1) has been demonstrated to play a crucial role. In this study, we have focused on a 2.2 kb sequence of the regulatory region located upstream of the GFAP gene, searching in a panel of control individuals for single-nucleotide polymorphisms (SNPs) that could modulate GFAP transcription. Among four SNPs of the GFAP promoter whose alleles have been predicted by in silico analysis to induce differences in the pattern of binding transcription factors, we have identified a new AP-1 binding site lying at −250 bp upstream from the GFAP transcriptional start site. The two alleles of this polymorphic locus have shown to bind the AP-1 complex to different extents, thus promoting variable transcriptional activities of the GFAP promoter. Therefore, these SNP alleles may, among others, mediate the effects of GFAP mutations, thus explaining the phenotypic heterogeneity of Alexander disease.
机译：总结胶质纤维酸性蛋白（GFAP）基因编码属于中间丝家族的细胞骨架蛋白，其表达被认为是星形胶质细胞分化的标志。 GFAP的表达由于脑胶质增生而被上调，它依赖于激素，生长因子，细胞因子和转录因子，并且在这些因子中，激活蛋白1（AP-1）已被证明发挥关键作用。在这项研究中，我们专注于位于GFAP基因上游的2.2 kb调控区域序列，在一组对照个体中搜索可以调节GFAP转录的单核苷酸多态性（SNP）。在通过计算机分析预测其等位基因会诱导结合转录因子模式差异的GFAP启动子的四个SNP中，我们确定了一个新的AP-1结合位点，位于GFAP转录起始位点上游-250 bp。已显示该多态性基因座的两个等位基因以不同程度结合AP-1复合物，从而促进了GFAP启动子的可变转录活性。因此，这些SNP等位基因可能介导了GFAP突变的影响，从而解释了亚历山大病的表型异质性。

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