Exploring the interplay between enhancer-promoter interactions and transcription

Enhancers in metazoan genomes are known to activate their target genes across both short and long genomic distances. Recent advances in chromosome conformation capture assays and single-cell imaging have shed light on the underlying chromatin contacts and dynamics. Yet the relationship between 3D physical enhancer-promoter (E-P) interactions and transcriptional activation remains unresolved. In this brief review, we discuss recent studies exploring this relationship across scales: from developmental stages to the minutes surrounding transcriptional activation and from the tissue level to single-allele subcellular dynamics. We discuss how seemingly contradictory observations might be reconciled and contribute to a refined causal relationship between E-P interactions and transcription, with mutual influences.