Ma D, Armugam A, Jeyaseelan K
Department of Biochemistry, Faculty of Medicine, National University of Singapore, Singapore.
Eur J Biochem. 2001 Mar;268(6):1844-50. doi: 10.1046/j.1432-1033.2001.02059.x.
This report is the first study of the regulation of expression of a toxin gene and it also demonstrates the novel finding that the cardiotoxin (CTX)-2 gene from Naja sputatrix is expressed in the venom gland as well as in other tissues in the snake, such as liver, heart and muscle. The venom gland produces a 500-bp (spliced) CTX-2 mRNA as the final transcript. However, the liver produces two types of CTX-2 mRNA, of which the unspliced transcript (1 kb) is predominant; the 500 bp spliced transcript is the minor species. This differential expression of the CTX gene has been attributed to the usage of alternative promoter consisting of independent TATA boxes and corresponding transcription initiation sites. Among the several transcription factors that have been identified by a search of the TFIID database, the participation of two glucocorticoid elements in the expression of the CTX gene has been demonstrated by promoter deletion analysis. Putative binding sites for SP-1, C/EBP, CACCC-binding factor and at least two unknown binding factors have also been identified by DNase I footprinting of the promoter.
本报告是对毒素基因表达调控的首次研究，同时还展示了一项新发现，即来自喷毒眼镜蛇（Naja sputatrix）的心脏毒素（CTX）-2基因在毒腺以及蛇的其他组织（如肝脏、心脏和肌肉）中均有表达。毒腺产生一种500个碱基对（剪接后）的CTX-2 mRNA作为最终转录本。然而，肝脏产生两种类型的CTX-2 mRNA，其中未剪接的转录本（1 kb）占主导；500个碱基对的剪接转录本是次要类型。CTX基因的这种差异表达归因于由独立TATA盒和相应转录起始位点组成的替代启动子的使用。在通过搜索TFIID数据库鉴定出的几种转录因子中，通过启动子缺失分析证明了两个糖皮质激素元件参与CTX基因的表达。通过启动子的DNase I足迹分析还鉴定出了SP-1、C/EBP、CACCC结合因子以及至少两个未知结合因子的假定结合位点。
