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

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.

Enhancer RNAs participate in androgen receptor-driven looping that selectively enhances gene activation

“…2B and Fig. S2 A-E), consistent with the notion that ligand-activated eRNAs are important for nearby gene activation (13,17). Considering that KLK15, 2, and 4 were adjacent to KLK3 and androgen-responsive ( Fig.…”

“…Although eRNAs are bidirectional and nonpolyadenylated, their induction correlates with the induction of adjacent exon-coding genes (9). The activity of eRNAs was shown to augment the expression of not only neighboring but also intrachromosomally distant genes to convey enhancer-dependent transcription (12,13). Recently, the 5′-GRO-seq data have revealed that sequencespecific transcription factors and eRNA transcripts are required for transfer of full enhancer activity to a target promoter (14).…”

A long non-coding RNA transcribed from conserved non-coding sequences contributes to the mouse prolyl oligopeptidase gene activation

“…Some enhancer-like RNAs were reported to interact with mediators and change the chromatin conformation to activate the target genes (60). eRNAs have been reported to establish the chromatin looping and generate the interaction of the enhancers with their target genes (61)(62)(63). In the current study, the lncPrep+96kb knockdown did not change the histone acetylation pattern in the Hepa1-6 cell (Fig.…”

Critical roles of long noncoding RNAs in Drosophila spermatogenesis

“…Some lncRNAs regulate the transcription of neighboring genes in a cis-acting manner (Lai et al 2013;Melo et al 2013), whereas others regulate gene expression in trans, e.g., the TP53-induced lncRNAs Dlx6os1 and Hotair (Feng et al 2006;Huarte et al 2010;Chu et al 2011). We showed that CR42858 could regulate the expression of neighboring genes as well as many more distant genes.…”