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Molecular and Cellular Biology, August 2008, p. 4772-4781, Vol. 28, No. 15
0270-7306/08/$08.00+0     doi:10.1128/MCB.00323-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Polycomb Complex 2 Is Required for E-cadherin Repression by the Snail1 Transcription Factor{triangledown} ,{dagger}

Nicolás Herranz,1 Diego Pasini,2 Víctor M. Díaz,1 Clara Francí,1 Arantxa Gutierrez,3 Natàlia Dave,1 Maria Escrivà,1 Inma Hernandez-Muñoz,1 Luciano Di Croce,3 Kristian Helin,2 Antonio García de Herreros,1,4* and Sandra Peiró1*

Programa de Recerca en Càncer, IMIM-Hospital del Mar, Barcelona, Spain,1 Biotech Research and Innovation Centre (BRIC) and Center for Epigenetics, University of Copenhagen, Copenhagen, Denmark,2 ICREA and Centre de Regulació Genòmica, Barcelona, Spain,3 Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain4

Received 26 February 2008/ Returned for modification 2 April 2008/ Accepted 21 May 2008

The transcriptional factor Snail1 is a repressor of E-cadherin (CDH1) gene expression essential for triggering epithelial-mesenchymal transition. Snail1 represses CDH1, directly binding its promoter and inducing the synthesis of the Zeb1 repressor. In this article, we show that repression of CDH1 by Snail1, but not by Zeb1, is dependent on the activity of Polycomb repressive complex 2 (PRC2). Embryonic stem (ES) cells null for Suz12, one of the components of PRC2, show higher levels of Cdh1 mRNA than control ES cells. In tumor cells, interference of PRC2 activity prevents the ability of Snail1 to downregulate CDH1 and partially derepresses CDH1. Chromatin immunoprecipitation assays demonstrated that Snail1 increases the binding of Suz12 to the CDH1 promoter and the trimethylation of lysine 27 in histone H3. 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.

* Corresponding author. Mailing address: Institut Municipal d'Investigació Mèdica, Parc de Recerca Biomèdica de Barcelona, c/ Dr. Aiguader 88, E-08003 Barcelona, Spain. Phone: 34-93-316-0433. Fax: 34-93-316-0410. E-mail for Antonio García de Herreros: agarcia{at}imim.es. E-mail for Sandra Peiró: speiro{at}imim.es

{triangledown} Published ahead of print on 2 June 2008.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, August 2008, p. 4772-4781, Vol. 28, No. 15
0270-7306/08/$08.00+0     doi:10.1128/MCB.00323-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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