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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.<\/jats:p>","DOI":"10.1038\/ncomms7520","type":"journal-article","created":{"date-parts":[[2015,3,27]],"date-time":"2015-03-27T10:06:44Z","timestamp":1427450804000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":152,"title":["Genome-wide profiling of p53-regulated enhancer RNAs uncovers a subset of enhancers controlled by a lncRNA"],"prefix":"10.1038","volume":"6","author":[{"given":"Nicolas","family":"L\u00e9veill\u00e9","sequence":"first","affiliation":[]},{"given":"Carlos A.","family":"Melo","sequence":"additional","affiliation":[]},{"given":"Koos","family":"Rooijers","sequence":"additional","affiliation":[]},{"given":"Angel","family":"D\u00edaz-Lagares","sequence":"additional","affiliation":[]},{"given":"Sonia A.","family":"Melo","sequence":"additional","affiliation":[]},{"given":"Gozde","family":"Korkmaz","sequence":"additional","affiliation":[]},{"given":"Rui","family":"Lopes","sequence":"additional","affiliation":[]},{"given":"Farhad Akbari","family":"Moqadam","sequence":"additional","affiliation":[]},{"given":"Ana R.","family":"Maia","sequence":"additional","affiliation":[]},{"given":"Patrick J.","family":"Wijchers","sequence":"additional","affiliation":[]},{"given":"Geert","family":"Geeven","sequence":"additional","affiliation":[]},{"given":"Monique L.","family":"den Boer","sequence":"additional","affiliation":[]},{"given":"Raghu","family":"Kalluri","sequence":"additional","affiliation":[]},{"given":"Wouter","family":"de Laat","sequence":"additional","affiliation":[]},{"given":"Manel","family":"Esteller","sequence":"additional","affiliation":[]},{"given":"Reuven","family":"Agami","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2015,3,27]]},"reference":[{"key":"BFncomms7520_CR1","doi-asserted-by":"publisher","first-page":"1227","DOI":"10.1038\/1921227a0","volume":"192","author":"FH Crick","year":"1961","unstructured":"Crick, F. 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