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Title: | Genome-wide profiling of p53-regulated enhancer RNAs uncovers a subset of enhancers controlled by a lncRNA | Authors: | Léveillé, Nicolas Melo, Carlos A. Rooijers, Koos Díaz-Lagares, Angel Melo, Sonia A. Korkmaz, Gozde Lopes, Rui Moqadam, Farhad Akbari Maia, Ana R Wijchers, Patrick J. Geeven, Geert den Boer, Monique L. Kalluri, Raghu de Laat, Wouter Esteller, Manel Agami, Reuven |
Issue Date: | 27-Mar-2015 | Publisher: | Springer Nature | Project: | SFRH/BD/33472/2008 SFRH/BD/74476/2010; POPH/FSE) Human Frontiers Program to S.A.M Netherlands Organization for Scientific Research (‘NWO’ Vidi grant) to M.L.dB. F.A.M., ‘Sara Borrell’ postdoctoral contract (CD12/00738) from the ISCIII at the Spanish Ministry of Economy and Competitiveness to A.D.L., European Research Council (ERC) Advanced Grant EPINORC (# 268626) to M.E. European Research Council (ERC) Advanced Grant EnhReg to R.A. |
Serial title, monograph or event: | Nature Communications | Volume: | 6 | Issue: | 1 | Abstract: | 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. | URI: | https://hdl.handle.net/10316/109239 | ISSN: | 2041-1723 | DOI: | 10.1038/ncomms7520 | Rights: | openAccess |
Appears in Collections: | I&D CNC - Artigos em Revistas Internacionais |
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Genomewide-profiling-of-p53regulated-enhancer-RNAs-uncovers-a-subset-of-enhancers-controlled-by-a-lncRNANature-Communications.pdf | 1.54 MB | Adobe PDF | View/Open |
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