enhancerpromotor

Enhancer-promoter interactions are regulatory connections in which enhancers, distal DNA elements, modulate the activity of gene promoters to control transcription. They are a major mechanism for tissue- and stage-specific gene expression, enabling distant elements to influence promoters across large genomic distances.

Mechanism: Enhancers recruit sequence-specific transcription factors and coactivators such as Mediator and cohesin. Through chromatin looping, the enhancer is brought into proximity with its promoter, promoting recruitment of RNA polymerase II and general transcription factors. Active enhancers are often marked by H3K4me1 and H3K27ac, while promoters carry H3K4me3. Many enhancers produce bidirectional enhancer RNAs, though the function of eRNAs varies. Enhancer-promoter interactions are generally orientation- and distance-independent.

Genomic architecture: Most interactions occur within topologically associating domains (TADs) and are shaped by looping factors such as CTCF and cohesin. While many contacts stay within the same TAD, long-range interactions can occur, especially during development. Compatibility between enhancer motifs and promoter features influences regulatory output.

Impact and study: Disruptions to enhancer-promoter contacts can alter gene expression and contribute to development disorders and cancer. Researchers map these interactions with chromosome conformation capture methods (Hi-C, promoter capture Hi-C) and test function with CRISPR-based perturbations and high-throughput reporter assays (STARR-seq). Integrating genetic variation with epigenomic data helps interpret noncoding variants that affect enhancer-promoter activity.