Evidence that eRNAs cause downstream effects on the efficiency of enhancer activation and gene transcription suggests its functional capabilities and potential importance.
The transcription factor p53 has been demonstrated to bind enhancer regions and generate eRNAs in a p53-dependent manner. In cancer, p53 plays a central role in tumor suppression as mutations of the gene are shown to appear in 50% of tumors. These p53-bound enhancer regions (p53BERs) are shown to interact with multiple local and distal gene targets involved in cell proliferation and survival. Furthermore, eRNAs generated by the activation of p53BERs are shown to be required for efficient transcription of the p53 target genes, indicating the likely important regulatory role of eRNAs in tumor suppression and cancer. Generally, mutations in eRNA have been shown to demonstrate similar phenotypic behavior in oncogenesis as compared to protein-coding RNA.
Variations in enhancers have been implicated in human disease but a therapeutic approach to manipulate enhancer activity is currently not possible. With the emergence of eRNAs as important components in enhancer activity, powerful therapeutic tools such as RNAi may provide promising routes to target disruption of gene expression.