Enhancers are cis-regulatory elements that can activate transcription remotely to regulate a specific pattern of a gene's expression. Genes typically have many enhancers that are often intermingled in the loci of other genes. To regulate expression, enhancers must therefore activate their correct promoter while ignoring others that may be in closer linear proximity. In this review, we discuss mechanisms by which enhancers engage with promoters, including recent findings on the role of cohesin and the Mediator complex, and how this specificity in enhancer-promoter communication is encoded. Genetic dissection of model loci, in addition to more recent findings using genome-wide approaches, highlight the core promoter sequence, its accessibility, cofactor-promoter preference, in addition to the surrounding genomic context, as key components.
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