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; Sandra Peiró

doi:10.1128/MCB.00323-08

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, Sandra Peiró

299 Citations (Scopus)

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.

Original language	English
Journal	Molecular and Cellular Biology
Volume	28
Issue number	15
Pages (from-to)	4772-81
Number of pages	9
ISSN	0270-7306
DOIs	https://doi.org/10.1128/MCB.00323-08
Publication status	Published - Aug 2008

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@article{34526c30533211dd8d9f000ea68e967b,

title = "Polycomb complex 2 is required for E-cadherin repression by the Snail1 transcription factor.",

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.",

author = "Nicol{\'a}s Herranz and Diego Pasini and D{\'i}az, {V{\'i}ctor M} and Clara Franc{\'i} and Arantxa Gutierrez and Nat{\`a}lia Dave and Maria Escriv{\`a} and Inma Hernandez-Mu{\~n}oz and {Di Croce}, Luciano and Kristian Helin and {Garc{\'i}a de Herreros}, Antonio and Sandra Peir{\'o}",

year = "2008",

month = aug,

doi = "10.1128/MCB.00323-08",

language = "English",

volume = "28",

pages = "4772--81",

journal = "Molecular and Cellular Biology",

issn = "0270-7306",

publisher = "American Society for Microbiology",

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TY - JOUR

T1 - Polycomb complex 2 is required for E-cadherin repression by the Snail1 transcription factor.

AU - Herranz, Nicolás

AU - Pasini, Diego

AU - Díaz, Víctor M

AU - Francí, Clara

AU - Gutierrez, Arantxa

AU - Dave, Natàlia

AU - Escrivà, Maria

AU - Hernandez-Muñoz, Inma

AU - Di Croce, Luciano

AU - Helin, Kristian

AU - García de Herreros, Antonio

AU - Peiró, Sandra

PY - 2008/8

Y1 - 2008/8

N2 - 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.

AB - 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.

U2 - 10.1128/MCB.00323-08

DO - 10.1128/MCB.00323-08

M3 - Journal article

C2 - 18519590

SN - 0270-7306

VL - 28

SP - 4772

EP - 4781

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

IS - 15

ER -

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

Abstract

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