Genome-wide profiling of p53-regulated enhancer RNAs uncovers a subset of enhancers controlled by a lncRNA

• Type: Article in International Scientific Journal
• Date: 2015

Authors

Leveille, N (Author) Other; Melo, CA (Author) Other; Rooijers, K (Author) Other; Diaz Lagares, A (Author) Other; Melo, SA (Author) FMUP; Korkmaz, G (Author) Other; Lopes, R (Author) Other; Moqadam, FA (Author) Other; Maia, AR (Author) Other; Wijchers, PJ (Author) Other; Geeven, G (Author) Other; den Boer, ML (Author) Other; Kalluri, R (Author) Other; de Laat, W (Author) Other; Esteller, M (Author) Other; Agami, R (Author) Other

Journal

Title: Nature Communications

Vol. 6

Final page: 6520

ISSN: 2041-1723

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 132 Citations

Scopus - 135 Citations

Other information

Authenticus ID: P-00A-9F3

DOI: 10.1038/ncomms7520

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 12