The architecture of gene expression: integrating dispersed cis-regulatory modules into coherent regulatory domains

Specificity and precision of expression are essential for the genes that regulate developmental processes. The specialized cis-acting modules, such as enhancers, that define gene expression patterns can be distributed across large regions, raising questions about the nature of the mechanisms that underline their action. Recent data has exposed the structural 3D context in which these long-range enhancers are operating. Here, we present how these studies shed new light on principles driving long-distance regulatory relationships. We discuss the molecular mechanisms that enable and accompany the action of long-range acting elements and the integration of multiple distributed regulatory inputs into the coherent and specific regulatory programs that are key to embryonic development.