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

• Type: Article in International Scientific Journal
• Date: 2013

Authors

Melo, CA (Author) Other; Drost, J (Author) Other; Wijchers, PJ (Author) Other; van de Werken, H (Author) Other; de Wit, E (Author) Other; Vrielink, JAFO (Author) Other; Elkon, R (Author) Other; Melo, SA (Author) Other; Leveille, N (Author) Other; Kalluri, R (Author) Other; de Laat, W (Author) Other; Agami, R (Author) Other

Journal

The Journal is awaiting validation by the Administrative Services.

Title: MOLECULAR CELL

Vol. 49

Pages: 524-535

ISSN: 1097-2765

Indexing

ISI Web of Knowledge - 377 Citations

Scopus - 385 Citations

Other information

Authenticus ID: P-002-0J2

DOI: 10.1016/j.molcel.2012.11.021

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 12