2026-04-13T02:32:50Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/1255942025-12-05T09:34:02Zcom_2072_1057col_2072_478799col_2072_478916col_2072_478917

Genome-wide profiling of p53-regulated enhancer RNAs uncovers a subset of enhancers controlled by a lncRNA Léveillé, Nicolas Melo, Carlos A. Rooijers, Koos Diaz-Lagares, Angel Melo, Sónia Rita Cardoso, 1978- Korkmaz, Gozde Lopes, Rui Akbari Moqadam, Farhad Maia, Ana R. Wijchers, Patrick J. Geeven, Geert den Boer, Monique L. Kalluri, Raghu de Laat, Wouter Esteller, Manel Agami, Reuven Càncer Genoma humà Cancer Human genome p53 binds enhancers to regulate key target genes. Here, we globally mapped p53-regulated enhancers by looking at enhancer RNA (eRNA) production. Intriguingly, while many p53-induced enhancers contained p53-binding sites, most did not. As long non-coding RNAs(lncRNAs) are prominent regulators of chromatin dynamics, we hypothesized that p53-induced lncRNAs contribute to the activation of enhancers by p53. Among p53-induced lncRNAs, we identified LED and demonstrate that its suppression attenuates p53 function. Chromatin-binding and eRNA expression analyses show that LED associates with and activates strong enhancers. One prominent target of LED was located at an enhancer region within CDKN1A gene, a potent p53-responsive cell cycle inhibitor. LED knockdown reduces CDKN1A enhancer induction and activity, and cell cycle arrest following p53 activation. Finally, promoter-associated hypermethylation analysis shows silencing of LED in human tumours. Thus, our study identifies a new layer of complexity in the p53 pathway and suggests its dysregulation in cancer. 2018-10-24T12:53:10Z 2018-10-24T12:53:10Z 2015-03-27 2018-10-24T12:53:10Z info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Reproducció del document publicat a: https://doi.org/10.1038/ncomms7520 Nature Communications, 2015, vol. 6, p. 6520 https://doi.org/10.1038/ncomms7520 info:eu-repo/grantAgreement/EC/FP7/268626/EU//EPINORC cc-by (c) Léveillé, Nicolas et al., 2015 http://creativecommons.org/licenses/by/3.0/es info:eu-repo/semantics/openAccess Nature Publishing Group Articles publicats en revistes (Ciències Fisiològiques)