2026-06-14T03:54:52Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/261072025-12-18T12:56:00Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19617

00925njm 22002777a 4500 dc Sánchez-Molina, Sara author Estarás, Conchi author Oliva-Martinez, Jose Luis author Akizu, Naiara author Asensio-Juan, Elena author Rojas-Cabañeros, Jose Maria author Martínez-Balbás, Marian A author 2014-10 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. Sánchez-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. 10.1093/carcin/bgu111 1460-2180 0143-3334 Carcinogenesis 24853677 https://hdl.handle.net/20.500.12105/26107 Histone acetylation Ras transformation Gene expression Chromatin modification Regulation of CBP and Tip60 coordinates histone acetylation at local and global levels during Ras-induced transformation.