Tissue specific transcriptional regulation of mesangium-predominant gene, megsin

我们最近克隆了一个新的人类系膜优势基因Megsin的cDNA，它是丝氨酸超家族的一个新成员。本研究旨在探讨该基因在肾小球系膜细胞依赖表达的机制。Megsin基因定位于染色体18q21.3，与其他丝氨酸基因相近。该基因全长20kbp，蛇针超家族基因组结构高度保守。序列分析表明，在5^1-侧翼区有一个一致的启动子片段。不同细胞类型的报告分析表明，该区域在系膜细胞中具有很强的启动子活性。我们利用缺失突变和定点突变分析确定了两个积极的调控元件。电泳迁移率改变分析显示，有两个未知的转录因子与-129至-88区域结合。这些转录因子主要在系膜细胞中表达。综上所述，系膜细胞中巨蛋白的高水平可以通过转录因子的显性表达来解释。启动子中重要顺式元件的检测和这些转录因子在系膜细胞中的展示鼓励我们对该基因进行进一步的研究，以了解以系膜为主的基因表达。

We have recently cloned cDNA of a new human mesangium-predominant gene, megsin, which is a novel member of the serpin superfamily. The purpose of this study was to investigate the mechanisms of mesangial cell-dependent expression of this gene. The megsin gene was localized in chromosome 18q21.3, close to the other serpin genes. The gene spanned 20 kbp, and the genomic structure of the serpin superfamily was highly conserved. The sequence analysis demonstrated a consensus promoter segment within the 5^1-flanking region. Reporter assays in various cell types demonstrated strong promoter activity of this region in mesangial cells. We identified two positive regulatory elements, utilizing deletion mutagenesis and site-directed mutagenesis analysis. Electrophoretic mobility shift assays showed two unidentified transcription factors that bind to the -129 to -88 region. These transcription factors were predominantly expressed in mesangial cells. In Conclusion, high levels of megsin in mesangial cells could be explained by dominant expression of the transcription factors. Detection of the important cis-elements in the promoter and demonstration of these transcription factors in mesangial cells encourage us to perform further studies of this gene for understanding of mesangium-predominant gene expression.