Sánchez-Molina, SaraEstarás, ConchiOliva-Martinez, Jose LuisAkizu, NaiaraAsensio-Juan, ElenaRojas-Cabañeros, Jose MariaMartínez-Balbás, Marian A2025-01-232025-01-232014-10Sánchez-Molina S, Estarás C, Oliva JL, Akizu N, Asensio-Juan E, Rojas JM, Martínez-Balbás MA. Regulation of CBP and Tip60 coordinates histone acetylation at local and global levels during Ras-induced transformation. Carcinogenesis. 2014 Oct;35(10):2194-202.0143-3334https://hdl.handle.net/20.500.12105/26107Cell 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.engSMURhttp://creativecommons.org/licenses/by-nc-nd/4.0/Histone acetylationRas transformationGene expressionChromatin modificationAcetylationAnimalsCREB-Binding ProteinCell Transformation, NeoplasticChromatinCyclin-Dependent Kinase Inhibitor p27Genes, rasHistone AcetyltransferasesHistonesLysine Acetyltransferase 5MiceNIH 3T3 CellsPhosphatidylinositol 3-KinasesPromoter Regions, GeneticSignal TransductionTrans-ActivatorsAttribution-NonCommercial-NoDerivatives 4.0 International2485367735102194-220210.1093/carcin/bgu1111460-2180Carcinogenesisopen access