eRNAs Are Required for p53-Dependent Enhancer Activity and Gene Transcription

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 know...

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Bibliographic Details
Published in:Molecular cell 2013-02, Vol.49 (3), p.524-535
Main Authors: Melo, Carlos A., Drost, Jarno, Wijchers, Patrick J., van de Werken, Harmen, de Wit, Elzo, Vrielink, Joachim A.F. Oude, Elkon, Ran, Melo, Sónia A., Léveillé, Nicolas, Kalluri, Raghu, de Laat, Wouter, Agami, Reuven
Format: Article
Language:English
Subjects:
binding sites
cell cycle
Cell Cycle Checkpoints - genetics
Cell proliferation
Chromatin - metabolism
Chromosomes, Human - metabolism
Enhancer Elements, Genetic
Gene Expression Regulation, Neoplastic
Genes
Humans
MCF-7 Cells
Models, Genetic
Protein Binding - genetics
RNA
RNA - metabolism
RNA, Messenger - genetics
RNA, Messenger - metabolism
RNA, Untranslated - metabolism
transcription
transcription (genetics)
Transcription, Genetic
tumor suppressor genes
Tumor Suppressor Protein p53 - metabolism
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Summary: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. [Display omitted] ► p53BERs are p53-bound and p53-activity-dependent enhancer regions ► p53BERs interact intrachromosomally with multiple surrounding target genes ► p53BERs produce enhancer RNAs (eRNAs) in a p53-dependent manner ► eRNAs are involved in enhancement of target gene transcription and p53 function
ISSN:1097-2765
1097-4164
DOI:10.1016/j.molcel.2012.11.021