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Mol. Cell. Biol. doi:10.1128/MCB.00323-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Polycomb complex 2 is required for E-cadherin repression by the Snail1 transcription factor

Nicolás Herranz, Diego Pasini, Víctor M. Díaz, Clara Francí, Arantxa Gutierrez, Natàlia Dave, Maria Escrivà, Inma Hernandez-Muñoz, Luciano Di Croce, Kristian Helin, Antonio García de Herreros*, and Sandra Peiró*

Programa de Recerca en Càncer, IMIM-Hospital del Mar, Barcelona, Spain; Biotech Research and Innovation Centre (BRIC), Copenhagen, Denmark; ICREA and Centre de Regulació Genòmica, Barcelona, Spain; Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain

* To whom correspondence should be addressed. Email: agarcia{at}imim.es. speiro{at}imim.es.


  Abstract

The transcriptional factor Snail1 is a repressor of E-cadherin gene (CDH1) expression essential for triggering epithelial-mesenchymal transition (EMT). Snail1 represses CDH1 directly binding its promoter and inducing the synthesis of Zeb1 repressor. In this article we show that repression of CDH1 by Snail1, but not by Zeb1, is dependent on the activity of the Polycomb repressive complex 2 (PRC2). ES cells null for Suz12, one of the components of PRC2, show higher levels of Cdh1 mRNA than control ES cells. In tumour cells, interference of PRC2 activity prevents the ability of Snail1 to down-regulate CDH1 and partially de-represses CDH1. Chromatin immunoprecipitation assays demonstrated that Snail1 increases the binding of Suz12 to CDH1 promoter and the tri-methylation of lysine 27 in the histone 3. Moreover, Snail1 interacts with Suz12 and Ezh2 as shown by coimmunoprecipitation experiments. In conclusion these results demonstrate that Snail1 recruits PRC2 to the CDH1 promoter and requires the activity of this complex to repress E-cadherin expression.






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