eRNAs are required for p53-dependent enhancer activity and gene transcription

Carlos A Melo, Jarno Drost, Patrick J Wijchers, Harmen van de Werken, Elzo de Wit, Joachim A F Oude Vrielink, Ran Elkon, Sónia A Melo, Nicolas Léveillé, Raghu Kalluri, Wouter de Laat, Reuven Agami

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review


Binding within or nearby target genes involved in cell proliferation and survival enables the p53 tumor suppressor gene to regulate their transcription and cell-cycle progression. Using genome-wide chromatin-binding profiles, we describe binding of p53 also to regions located distantly from any known p53 target gene. Interestingly, many of these regions possess conserved p53-binding sites and all known hallmarks of enhancer regions. We demonstrate that these p53-bound enhancer regions (p53BERs) indeed contain enhancer activity and interact intrachromosomally with multiple neighboring genes to convey long-distance p53-dependent transcription regulation. Furthermore, p53BERs produce, in a p53-dependent manner, enhancer RNAs (eRNAs) that are required for efficient transcriptional enhancement of interacting target genes and induction of a p53-dependent cell-cycle arrest. Thus, our results ascribe transcription enhancement activity to p53 with the capacity to regulate multiple genes from a single genomic binding site. Moreover, eRNA production from p53BERs is required for efficient p53 transcription enhancement.

Originele taal-2Engels
Pagina's (van-tot)524-35
Aantal pagina's12
TijdschriftMolecular cell
Nummer van het tijdschrift3
StatusGepubliceerd - 7 feb. 2013


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