Long distance relationships: Enhancer–promoter communication and dynamic gene transcription

The three-dimensional regulation of gene transcription involves loop formation between enhancer and promoter elements, controlling spatiotemporal gene expression in multicellular organisms. Enhancers are usually located in non-coding DNA and can activate gene transcription by recruiting transcription factors, chromatin remodeling factors and RNA Polymerase II. Research over the last few years has revealed that enhancers have tell-tale characteristics that facilitate their detection by several approaches, although the hallmarks of enhancers are not always uniform. Enhancers likely play an important role in the activation of genes by functioning as a primary point of contact for transcriptional activators, and by making physical contact with gene promoters often by means of a chromatin loop. Although numerous transcriptional regulators participate in the formation of chromatin loops that bring enhancers into proximity with promoters, the mechanism(s) of enhancer–promoter connectivity remain enigmatic. Here we discuss enhancer function, review some of the many proteins shown to be involved in establishing enhancer–promoter loops, and describe the dynamics of enhancer–promoter contacts during development, differentiation and in specific cell types.