Peiró Sandra, Escrivà Maria, Puig Isabel, Barberà Maria José, Dave Natàlia, Herranz Nicolás, Larriba Maria Jesús, Takkunen Minna, Francí Clara, Muñoz Alberto, Virtanen Ismo, Baulida Josep, García de Herreros Antonio
Unitat de Biologia Cellular i Molecular, Institut Municipal d'Investigació Mèdica, Universitat Pompeu Fabra, c/ Doctor Aiguader, 80, 08003 Barcelona, Spain.
Nucleic Acids Res. 2006 Apr 14;34(7):2077-84. doi: 10.1093/nar/gkl141. Print 2006.
The product of Snail1 gene is a transcriptional repressor of E-cadherin expression and an inductor of the epithelial-mesenchymal transition in several epithelial tumour cell lines. Transcription of Snail1 is induced when epithelial cells are forced to acquire a mesenchymal phenotype. In this work we demonstrate that Snail1 protein limits its own expression: Snail1 binds to an E-box present in its promoter (at -146 with respect to the transcription start) and represses its activity. Therefore, mutation of the E-box increases Snail1 transcription in epithelial and mesenchymal cells. Evidence of binding of ectopic or endogenous Snail1 to its own promoter was obtained by chromatin immunoprecipitation (ChIP) experiments. Studies performed expressing different forms of Snail1 under the control of its own promoter demonstrate that disruption of the regulatory loop increases the cellular levels of Snail protein. These results indicate that expression of Snail1 gene can be regulated by its product and evidence the existence of a fine-tuning feed-back mechanism of regulation of Snail1 transcription.
Snail1基因的产物是E-钙黏蛋白表达的转录抑制因子，也是几种上皮肿瘤细胞系上皮-间质转化的诱导因子。当上皮细胞被迫获得间质表型时，Snail1的转录被诱导。在这项研究中，我们证明Snail1蛋白限制其自身的表达：Snail1与存在于其启动子中的一个E-盒（相对于转录起始位点在-146处）结合并抑制其活性。因此，E-盒的突变会增加上皮细胞和间质细胞中Snail1的转录。通过染色质免疫沉淀（ChIP）实验获得了异位或内源性Snail1与其自身启动子结合的证据。在其自身启动子控制下表达不同形式Snail1的研究表明，调节环的破坏会增加Snail蛋白的细胞水平。这些结果表明，Snail1基因的表达可受其产物调控，并证明存在一种对Snail1转录进行精细调节的反馈机制。
