Long noncoding RNAs usher in a new era in the biology of enhancers

Abstract

Enhancer-associated long noncoding RNAs act over long distances and across chromosomes to activate transcription at distal promoters. Here, we address the latest advances made toward understanding the role of long noncoding RNA expression and the involvement of these RNAs in enhancer function through association with protein factors and modulation of chromatin structure.

Figure 1. Long noncoding RNAs in enhancer looping and function

Long noncoding RNAs are proposed to function in the establishment or maintenance of enhancer promoter looping and activation of gene expression. In the absence of looping interactions (upper left), the enhancer is inactive and transcription is minimal. One model for activation (counter-clockwise) features engagement of enhancer binding factors, transcription factors and bridging factors such as the Mediator, Cohesin and WDR5 complexes (lower left), which leads to gene looping between enhancer and promoter sequences followed by induction of long noncoding RNA expression and transcriptional activation of the target gene (lower right). A second model proposes that long noncoding RNA transcription precedes target gene activation and looping (clockwise), where binding of enhancer binding factors and transcription of long noncoding RNAs are the first steps in the activation process (upper right). Subsequently, a loop to the promoter is established through interactions with the transcription factors and bridging factors (lower right), leading to activation of the neighboring gene.