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Mol Cell. 2013 Feb 7;49(3):524-35. doi: 10.1016/j.molcel.2012.11.021. Epub 2012 Dec 27.

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

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  • 1Division of Gene Regulation, the Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, the Netherlands; Doctoral Programme in Biomedicine and Experimental Biology, Centre for Neuroscience and Cell Biology, 3004-517 Coimbra, Portugal.

Abstract

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.

Copyright © 2013 Elsevier Inc. All rights reserved.

PMID:
23273978
[PubMed - indexed for MEDLINE]
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