eRNA binding produces tailored CBP activity profiles to regulate gene expression

Abstract

Enhancers are cis- regulatory genetic elements crucial for controlling temporal and cell-type specific patterns of gene expression. Active enhancers generate bi-directional non-coding RNA transcripts called enhancer RNAs (eRNAs). eRNAs are important for stimulating gene expression, but precise mechanisms for this ability remain unclear. Here we highlight recent findings that demonstrate a direct interaction between RNAs and the transcriptional co-activator Creb-binding protein (CBP). Notably, RNA binding could stimulate the core histone acetyltransferase activity of the enzyme, observable in cells as a link between eRNA production, CBP-dependent histone acetylation and expression of genes regulated by specific enhancers. Although RNA binding was independent of RNA sequence, specificity arises in a locus-specific manner at transcribed sites where CBP was bound to chromatin. The results suggest a functional role for eRNAs as regulatory molecules that are able to stimulate the activity of a key epigenetic regulatory enzyme, thereby promoting gene expression. Furthermore, they suggest an intriguing role for eRNAs: by modulating the activity of chromatin modifying enzymes, they could directly impact transcription by altering the chromatin environment.