Regulation of CBP and Tip60 coordinates histone acetylation at local and global levels during Ras-induced transformation.

Cell transformation is clearly linked to epigenetic changes. However, the role of the histone-modifying enzymes in this process is still poorly understood. In this study, we investigated the contribution of the histone acetyltransferase (HAT) enzymes to Ras-mediated transformation. Our results demon...

Descripción completa

Detalles Bibliográficos
Autores: Sánchez-Molina, Sara, Estarás, Conchi, Oliva-Martinez, Jose Luis, Akizu, Naiara, Asensio-Juan, Elena, Rojas-Cabañeros, Jose Maria, Martínez-Balbás, Marian A
Tipo de recurso: artículo
Fecha de publicación:2014
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/26107
Acceso en línea:https://hdl.handle.net/20.500.12105/26107
Access Level:acceso abierto
Palabra clave:Histone acetylation
Ras transformation
Gene expression
Chromatin modification
Acetylation
Animals
CREB-Binding Protein
Cell Transformation, Neoplastic
Chromatin
Cyclin-Dependent Kinase Inhibitor p27
Genes, ras
Histone Acetyltransferases
Histones
Lysine Acetyltransferase 5
Mice
NIH 3T3 Cells
Phosphatidylinositol 3-Kinases
Promoter Regions, Genetic
Signal Transduction
Trans-Activators
id ES_6eddf8a0d10e1a6cf4ce0cf4b45a86ff
oai_identifier_str oai:repisalud.isciii.es:20.500.12105/26107
network_acronym_str ES
network_name_str España
repository_id_str
spelling Regulation of CBP and Tip60 coordinates histone acetylation at local and global levels during Ras-induced transformation.Sánchez-Molina, SaraEstarás, ConchiOliva-Martinez, Jose LuisAkizu, NaiaraAsensio-Juan, ElenaRojas-Cabañeros, Jose MariaMartínez-Balbás, Marian AHistone acetylationRas transformationGene expressionChromatin modificationAcetylationAnimalsCREB-Binding ProteinCell Transformation, NeoplasticChromatinCyclin-Dependent Kinase Inhibitor p27Genes, rasHistone AcetyltransferasesHistonesLysine Acetyltransferase 5MiceNIH 3T3 CellsPhosphatidylinositol 3-KinasesPromoter Regions, GeneticSignal TransductionTrans-ActivatorsCell transformation is clearly linked to epigenetic changes. However, the role of the histone-modifying enzymes in this process is still poorly understood. In this study, we investigated the contribution of the histone acetyltransferase (HAT) enzymes to Ras-mediated transformation. Our results demonstrated that lysine acetyltransferase 5, also known as Tip60, facilitates histone acetylation of bulk chromatin in Ras-transformed cells. As a consequence, global H4 acetylation (H4K8ac and H4K12ac) increases in Ras-transformed cells, rendering a more decompacted chromatin than in parental cells. Furthermore, low levels of CREB-binding protein (CBP) lead to hypoacetylation of retinoblastoma 1 (Rb1) and cyclin-dependent kinase inhibitor 1B (Cdkn1b or p27Kip1) tumour suppressor gene promoters to facilitate Ras-mediated transformation. In agreement with these data, overexpression of Cbp counteracts Ras transforming capability in a HAT-dependent manner. Altogether our results indicate that CBP and Tip60 coordinate histone acetylation at both local and global levels to facilitate Ras-induced transformation.Oxford University PressMinisterio de Educación y Ciencia (España)Fundación La Marató TV3Instituto de Salud Carlos IIIRed Temática de Investigación Cooperativa en Cáncer (RTICC) (España)Government of Catalonia (España)Innovate UKFondation Jérôme-Lejeune20252025-01-2320142014-10-0120142014-10-01research articlehttp://purl.org/coar/resource_type/c_2df8fbb1SMURhttp://purl.org/coar/version/c_71e4c1898caa6e32info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.12105/26107reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)InglésengMinisterio de Educación y Ciencia Not available BFU2006-01493 MECANISMOS EPIGENETICOS IMPLICADOS EN LA PROLIFERACION Y DIFERENCION CELULARES: PAPEL DE LAS MODIFICACIONES DE LAS HISTONASES CSD2006-00049 Not availableES BFU-2012-34261 Not availableES PI09 0562Ministerio de Educación y Ciencia Not available SAF2006-04247 ANALISIS DE LOS MECANISMOS DE REGULACION DE LAS VIAS DE TRANSMISION DE SEÑALES DEPENDIENTES DE LAS PROTEINAS RAS: EFECTOS DIFERENCIALES, SISTEMAS DOCKING%2FSCAFFOLD Y NUEVOS ESTIMULOSMinisterio de Sanidad y Consumo Not available RD06%2F0020%2F0003 RED TEMÁTICA DE INVESTIGACIÓN COOPERATIVA DEL CANCERES RD12 0036open accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/261072026-06-12T12:43:37Z
dc.title.none.fl_str_mv Regulation of CBP and Tip60 coordinates histone acetylation at local and global levels during Ras-induced transformation.
title Regulation of CBP and Tip60 coordinates histone acetylation at local and global levels during Ras-induced transformation.
spellingShingle Regulation of CBP and Tip60 coordinates histone acetylation at local and global levels during Ras-induced transformation.
Sánchez-Molina, Sara
Histone acetylation
Ras transformation
Gene expression
Chromatin modification
Acetylation
Animals
CREB-Binding Protein
Cell Transformation, Neoplastic
Chromatin
Cyclin-Dependent Kinase Inhibitor p27
Genes, ras
Histone Acetyltransferases
Histones
Lysine Acetyltransferase 5
Mice
NIH 3T3 Cells
Phosphatidylinositol 3-Kinases
Promoter Regions, Genetic
Signal Transduction
Trans-Activators
title_short Regulation of CBP and Tip60 coordinates histone acetylation at local and global levels during Ras-induced transformation.
title_full Regulation of CBP and Tip60 coordinates histone acetylation at local and global levels during Ras-induced transformation.
title_fullStr Regulation of CBP and Tip60 coordinates histone acetylation at local and global levels during Ras-induced transformation.
title_full_unstemmed Regulation of CBP and Tip60 coordinates histone acetylation at local and global levels during Ras-induced transformation.
title_sort Regulation of CBP and Tip60 coordinates histone acetylation at local and global levels during Ras-induced transformation.
dc.creator.none.fl_str_mv Sánchez-Molina, Sara
Estarás, Conchi
Oliva-Martinez, Jose Luis
Akizu, Naiara
Asensio-Juan, Elena
Rojas-Cabañeros, Jose Maria
Martínez-Balbás, Marian A
author Sánchez-Molina, Sara
author_facet Sánchez-Molina, Sara
Estarás, Conchi
Oliva-Martinez, Jose Luis
Akizu, Naiara
Asensio-Juan, Elena
Rojas-Cabañeros, Jose Maria
Martínez-Balbás, Marian A
author_role author
author2 Estarás, Conchi
Oliva-Martinez, Jose Luis
Akizu, Naiara
Asensio-Juan, Elena
Rojas-Cabañeros, Jose Maria
Martínez-Balbás, Marian A
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Educación y Ciencia (España)
Fundación La Marató TV3
Instituto de Salud Carlos III
Red Temática de Investigación Cooperativa en Cáncer (RTICC) (España)
Government of Catalonia (España)
Innovate UK
Fondation Jérôme-Lejeune
dc.subject.none.fl_str_mv Histone acetylation
Ras transformation
Gene expression
Chromatin modification
Acetylation
Animals
CREB-Binding Protein
Cell Transformation, Neoplastic
Chromatin
Cyclin-Dependent Kinase Inhibitor p27
Genes, ras
Histone Acetyltransferases
Histones
Lysine Acetyltransferase 5
Mice
NIH 3T3 Cells
Phosphatidylinositol 3-Kinases
Promoter Regions, Genetic
Signal Transduction
Trans-Activators
topic Histone acetylation
Ras transformation
Gene expression
Chromatin modification
Acetylation
Animals
CREB-Binding Protein
Cell Transformation, Neoplastic
Chromatin
Cyclin-Dependent Kinase Inhibitor p27
Genes, ras
Histone Acetyltransferases
Histones
Lysine Acetyltransferase 5
Mice
NIH 3T3 Cells
Phosphatidylinositol 3-Kinases
Promoter Regions, Genetic
Signal Transduction
Trans-Activators
description Cell transformation is clearly linked to epigenetic changes. However, the role of the histone-modifying enzymes in this process is still poorly understood. In this study, we investigated the contribution of the histone acetyltransferase (HAT) enzymes to Ras-mediated transformation. Our results demonstrated that lysine acetyltransferase 5, also known as Tip60, facilitates histone acetylation of bulk chromatin in Ras-transformed cells. As a consequence, global H4 acetylation (H4K8ac and H4K12ac) increases in Ras-transformed cells, rendering a more decompacted chromatin than in parental cells. Furthermore, low levels of CREB-binding protein (CBP) lead to hypoacetylation of retinoblastoma 1 (Rb1) and cyclin-dependent kinase inhibitor 1B (Cdkn1b or p27Kip1) tumour suppressor gene promoters to facilitate Ras-mediated transformation. In agreement with these data, overexpression of Cbp counteracts Ras transforming capability in a HAT-dependent manner. Altogether our results indicate that CBP and Tip60 coordinate histone acetylation at both local and global levels to facilitate Ras-induced transformation.
publishDate 2014
dc.date.none.fl_str_mv 2014
2014-10-01
2014
2014-10-01
2025
2025-01-23
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
SMUR
http://purl.org/coar/version/c_71e4c1898caa6e32
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.12105/26107
url https://hdl.handle.net/20.500.12105/26107
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Ministerio de Educación y Ciencia Not available BFU2006-01493 MECANISMOS EPIGENETICOS IMPLICADOS EN LA PROLIFERACION Y DIFERENCION CELULARES: PAPEL DE LAS MODIFICACIONES DE LAS HISTONAS
ES CSD2006-00049 Not available
ES BFU-2012-34261 Not available
ES PI09 0562
Ministerio de Educación y Ciencia Not available SAF2006-04247 ANALISIS DE LOS MECANISMOS DE REGULACION DE LAS VIAS DE TRANSMISION DE SEÑALES DEPENDIENTES DE LAS PROTEINAS RAS: EFECTOS DIFERENCIALES, SISTEMAS DOCKING%2FSCAFFOLD Y NUEVOS ESTIMULOS
Ministerio de Sanidad y Consumo Not available RD06%2F0020%2F0003 RED TEMÁTICA DE INVESTIGACIÓN COOPERATIVA DEL CANCER
ES RD12 0036
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 International
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 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University Press
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_ 1869410454677225472
score 15.812429

Similares en LA Referencia