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
Descripción
Sumario: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.

Similares en LA Referencia