Abstract
Gene expression requires successful communication between enhancer and promoter regions, whose activities are regulated by a variety of factors and associated with distinct chromatin structures; in addition, functionally related genes and their regulatory repertoire tend to be arranged in the same subchromosomal regulatory domains. In this review, we discuss the importance of enhancers, especially clusters of enhancers (such as super-enhancers), as key regulatory hubs to integrate environmental cues and encode spatiotemporal instructions for genome expression, which are critical for a variety of biological processes governing mammalian development. Furthermore, we emphasize that the enhancer-promoter interaction landscape provides a critical context to understand the aetiologies and mechanisms behind numerous complex human diseases and provides new avenues for effective transcription-based interventions.