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

The 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...

ver descrição completa

Detalhes bibliográficos
Autores: Peinado, Hector, Ballestar, Esteban, Esteller, Manel, Cano, Amparo
Formato: artículo
Fecha de publicación:2004
País:España
Recursos:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/17962
Acesso em linha:http://hdl.handle.net/20.500.12105/17962
Access Level:acceso abierto
Palavra-chave:Animals
Cadherins
DNA-Binding Proteins
Gene Expression Regulation
Histone Deacetylase 2
Histone Deacetylases
Humans
Mice
Promoter Regions, Genetic
Repressor Proteins
id ES_3c8384fa2a263102faf9ae1f853f7543
oai_identifier_str oai:repisalud.isciii.es:20.500.12105/17962
network_acronym_str ES
network_name_str España
repository_id_str
spelling Snail mediates E-cadherin repression by the recruitment of the Sin3A/histone deacetylase 1 (HDAC1)/HDAC2 complex.Peinado, HectorBallestar, EstebanEsteller, ManelCano, AmparoAnimalsCadherinsDNA-Binding ProteinsGene Expression RegulationHistone Deacetylase 2Histone DeacetylasesHumansMicePromoter Regions, GeneticRepressor ProteinsThe 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.Taylor & Francis20242024-02-1220042004-01-0120042004-01-01journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articlehttp://hdl.handle.net/20.500.12105/17962reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/179622026-06-12T12:43:37Z
dc.title.none.fl_str_mv Snail mediates E-cadherin repression by the recruitment of the Sin3A/histone deacetylase 1 (HDAC1)/HDAC2 complex.
title Snail mediates E-cadherin repression by the recruitment of the Sin3A/histone deacetylase 1 (HDAC1)/HDAC2 complex.
spellingShingle Snail mediates E-cadherin repression by the recruitment of the Sin3A/histone deacetylase 1 (HDAC1)/HDAC2 complex.
Peinado, Hector
Animals
Cadherins
DNA-Binding Proteins
Gene Expression Regulation
Histone Deacetylase 2
Histone Deacetylases
Humans
Mice
Promoter Regions, Genetic
Repressor Proteins
title_short Snail mediates E-cadherin repression by the recruitment of the Sin3A/histone deacetylase 1 (HDAC1)/HDAC2 complex.
title_full Snail mediates E-cadherin repression by the recruitment of the Sin3A/histone deacetylase 1 (HDAC1)/HDAC2 complex.
title_fullStr Snail mediates E-cadherin repression by the recruitment of the Sin3A/histone deacetylase 1 (HDAC1)/HDAC2 complex.
title_full_unstemmed Snail mediates E-cadherin repression by the recruitment of the Sin3A/histone deacetylase 1 (HDAC1)/HDAC2 complex.
title_sort Snail mediates E-cadherin repression by the recruitment of the Sin3A/histone deacetylase 1 (HDAC1)/HDAC2 complex.
dc.creator.none.fl_str_mv Peinado, Hector
Ballestar, Esteban
Esteller, Manel
Cano, Amparo
author Peinado, Hector
author_facet Peinado, Hector
Ballestar, Esteban
Esteller, Manel
Cano, Amparo
author_role author
author2 Ballestar, Esteban
Esteller, Manel
Cano, Amparo
author2_role author
author
author
dc.contributor.none.fl_str_mv
dc.subject.none.fl_str_mv Animals
Cadherins
DNA-Binding Proteins
Gene Expression Regulation
Histone Deacetylase 2
Histone Deacetylases
Humans
Mice
Promoter Regions, Genetic
Repressor Proteins
topic Animals
Cadherins
DNA-Binding Proteins
Gene Expression Regulation
Histone Deacetylase 2
Histone Deacetylases
Humans
Mice
Promoter Regions, Genetic
Repressor Proteins
description The 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.
publishDate 2004
dc.date.none.fl_str_mv 2004
2004-01-01
2004
2004-01-01
2024
2024-02-12
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12105/17962
url http://hdl.handle.net/20.500.12105/17962
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Taylor & Francis
publisher.none.fl_str_mv Taylor & Francis
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869406380385894400
score 15,198674

Registos relacionados