Peinado, HectorBallestar, EstebanEsteller, ManelCano, Amparo2024-02-122024-02-122004-01Mol Cell Biol . 2004 ;24(1):306-19.0270-7306http://hdl.handle.net/20.500.12105/17962The 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.engVoRhttp://creativecommons.org/licenses/by-nc-nd/4.0/AnimalsCadherinsDNA-Binding ProteinsGene Expression RegulationHistone Deacetylase 2Histone DeacetylasesHumansMicePromoter Regions, GeneticRepressor ProteinsAttribution-NonCommercial-NoDerivatives 4.0 Internacional1467316424130610.1128/MCB.24.1.306-319.2004Molecular and cellular biologyhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC303344/open access