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首页> 外文期刊>Gene expression >The first intron of the human osteopontin gene contains a C/EBP-beta-responsive enhancer.
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The first intron of the human osteopontin gene contains a C/EBP-beta-responsive enhancer.

机译：人骨桥蛋白基因的第一个内含子含有C / EBP-beta响应增强子。

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摘要

The osteopontin (OPN) protein is found expressed at high level in several processes including fibrotic evolution of organ injuries, tumorigenesis, and immune response. The molecular mechanisms that underly overexpression, especially at the transcriptional level, have been only partially clarified. Therefore, this study was undertaken in search for additional DNA elements in the regulatory regions of the OPN gene and cognate transcription factors. Our results on the region upstream of the transcription start site confirmed that essential elements are located within the first 100 bp. Analysis of the sequence that includes the first untranslated exon and first intron revealed that it could enhance the promoter activity. Experiments of transfection of constructs containing different fragments of this sequence showed that most of the enhancer activity was confined in the terminal 30-bp tract of the first intron, although it was not functioning in a myofibroblast cell line. DNA/protein binding assays and cotransfection experiments showed that the C/EBP-beta transcription factor was able to bind a recognition sequence in this 30-bp segment. We found a bi-allelic sequence polymorphism at +245 in the first intron, which did not show a significant functional effect, but is a useful tool for future association studies.
机译：发现骨桥蛋白（OPN）蛋白在多个过程中高水平表达，包括器官损伤的纤维化演变，肿瘤发生和免疫反应。过度表达的分子机制，尤其是在转录水平上，仅被部分阐明。因此，进行这项研究是为了寻找OPN基因调控区和相关转录因子中的其他DNA元件。我们在转录起始位点上游区域的结果证实，必需元件位于前100 bp之内。对包括第一个未翻译的外显子和第一个内含子的序列的分析表明，它可以增强启动子活性。转染含有该序列不同片段的构建体的实验表明，大多数增强子活性都限制在第一个内含子的30 bp末端，尽管它在成肌纤维细胞系中不起作用。 DNA /蛋白质结合测定和共转染实验表明，C /EBP-β转录因子能够结合该30 bp片段中的识别序列。我们在第一个内含子的+245位点发现了一个双等位基因序列多态性，该基因多态性未显示出明显的功能作用，但却是未来关联研究的有用工具。

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