Enhancer

An enhancer is a cis-regulatory DNA element that increases transcription of its target gene. Enhancers can function at a distance from promoters, may be upstream, downstream, or within introns, and can act in either orientation. They are often located near the genes they regulate but can be megabases away or act through looping to contact the promoter.

Enhancers work by binding transcription factors, which recruit coactivators such as p300/CBP and the Mediator complex. This assembly facilitates the recruitment of RNA polymerase II at the promoter, typically aided by chromatin looping that brings the enhancer into proximity with the promoter. Enhancer activity is associated with chromatin features of open chromatin and histone modifications, notably H3K4me1 and H3K27ac, and enhancer RNA transcription (eRNAs) is observed in some cases.

Enhancer activity is highly tissue- and development-specific, determined by the repertoire of transcription factors present in a cell at a given time. Genome-wide maps of enhancers use techniques such as ChIP-seq for transcription factors and histone marks, and assays like ATAC-seq or DNase-seq to identify accessible regions. Functional testing often employs reporter assays, CRISPR-based perturbations, or chromatin conformation capture methods to link enhancers to their target genes. Enhancers can be intronic and may exhibit redundancy, including shadow enhancers that contribute to developmental robustness.

Genetic variation within enhancers can alter the expression of target genes and influence disease risk. Understanding enhancers is central to explaining how distant regulatory sequences control gene expression in development, physiology, and pathology.