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Title

Snail mediates E-cadherin repression by the recruitment of the Sin3A/histone deacetylase 1 (HDAC1)/HDAC2 complex

AuthorsPeinado, Héctor; Ballestar, Estéban; Esteller, Manel; Cano, Amparo
Issue DateJan-2004
PublisherAmerican Society for Microbiology
CitationMolecular and Cellular Biology 24(1): 306-319 (2004)
AbstractThe transcription factor Snail has been described as a direct repressor of E-cadherin expression during development and carcinogenesis; however, the specific mechanisms involved in this process remain largely unknown. Here we show that mammalian Snail requires histone deacetylase (HDAC) activity to repress E-cadherin promoter and that treatment with trichostatin A (TSA) is sufficient to block the repressor effect of Snail. Moreover, overexpression of Snail is correlated with deacetylation of histones H3 and H4 at the E-cadherin promoter, and TSA treatment in Snail-expressing cells reverses the acetylation status of histones. Additionally, we demonstrate that Snail interacts in vivo with the E-cadherin promoter and recruits HDAC activity. Most importantly, we demonstrate an interaction between Snail, histone deacetylase 1 (HDAC1) and HDAC2, and the corepressor mSin3A. This interaction is dependent on the SNAG domain of Snail, indicating that the Snail transcription factor mediates the repression by recruitment of chromatin-modifying activities, forming a multimolecular complex to repress E-cadherin expression. Our results establish a direct causal relationship between Snail-dependent repression of E-cadherin and the modification of chromatin at its promoter.
Description14 pages, 7 figures.
Publisher version (URL)http://dx.doi.org/10.1128/MCB.24.1.306-319.2004
URIhttp://hdl.handle.net/10261/24647
DOI10.1128/MCB.24.1.306-319.2004
ISSN0270-7306
Appears in Collections:(IIBM) Artículos
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