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

作者：Melo Carlos A; Drost Jamo; Wijchers Patrick J; van de Werken Harmen; de Wit Elzo; Vrielink Joachim A F Oude; Elkon Ran; Melo Sonia A; Leveille Nicolas; Kalluri Raghu; de Laat Wouter; Agami Reuven^*

来源：Molecular Cell, 2013, 49(3): 524-535.

DOI：10.1016/j.molcel.2012.11.021

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.

• 出版日期2013-2-7