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

TY - JOUR

T1 - eRNAs are required for p53-dependent enhancer activity and gene transcription

AU - Melo, C.A.

AU - Drost, J.

AU - Wijchers, P.J.

AU - van de Werken, H.

AU - de Wit, E.

AU - Oude Vrielink, J.A.

AU - Elkon, R.

AU - Melo, S.A.

AU - Leveille, N.

AU - Kalluri, R.

AU - de Laat, W.

AU - Agami, R.

N1 - Reporting year: 2013

PY - 2013

Y1 - 2013

N2 - 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.

AB - 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.

U2 - 10.1016/j.molcel.2012.11.021

DO - 10.1016/j.molcel.2012.11.021

M3 - Article

SN - 1097-2765

VL - 49

SP - 524

EP - 535

JO - Molecular Cell

JF - Molecular Cell

IS - 3

ER -