Title:
|
Genome-wide profiling of p53-regulated enhancer RNAs uncovers a subset of enhancers controlled by a lncRNA
|
Author:
|
Léveillé, Nicolas; Melo, Carlos A.; Rooijers, Koos; Díaz Lagares, Angel; Melo, Sonia; 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
|
Other authors:
|
Universitat de Barcelona |
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. |
Subject(s):
|
-Càncer -Genoma humà -Cancer -Human genome |
Rights:
|
cc-by (c) Léveillé, Nicolas et al., 2015
http://creativecommons.org/licenses/by/3.0/es |
Document type:
|
Article Article - Published version |
Published by:
|
Nature Publishing Group
|
Share:
|
|