Published online 14 April 2006
Article |
Snail1 transcriptional repressor binds to its own promoter and controls its expression
Unitat de Biologia Cel·lular i Molecular, Institut Municipal d'Investigació Mèdica, Universitat Pompeu Fabra c/ Doctor Aiguader, 80; 08003 Barcelona, Spain 1 Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid c/ Arturo Duperier, 4; 28029 Madrid, Spain 2 Institute of Biomedicine/Anatomy, Biomedicum Helsinki, University of Helsinki Helsinki, Finland
*To whom correspondence should be addressed. Tel: 34 93 221 1009; Fax: 34 93 221 3237; Email: agarcia{at}imim.es
Received February 15, 2006. Revised March 16, 2006. Accepted March 16, 2006.
The product of Snail1 gene is a transcriptional repressor of E-cadherin expression and an inductor of the epithelialmesenchymal 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.
The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.
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