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

Title
Genome-wide profiling of p53-regulated enhancer RNAs uncovers a subset of enhancers controlled by a lncRNA
Type
Article in International Scientific Journal
Year
2015
Authors
Leveille, N
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Melo, CA
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Rooijers, K
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Diaz Lagares, A
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Melo, SA
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Korkmaz, G
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Lopes, R
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Moqadam, FA
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Maia, AR
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Wijchers, PJ
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Geeven, G
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den Boer, ML
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Kalluri, R
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de Laat, W
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Esteller, M
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Agami, R
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Journal
Title: Nature CommunicationsImported from Authenticus Search for Journal Publications
Vol. 6
Final page: 6520
ISSN: 2041-1723
Publisher: Springer Nature
Other information
Authenticus ID: P-00A-9F3
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
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