Figure 1. Enhancers activate transcription from any position relative to the promoter. A hypothetical gene (three exons shown as shaded boxes), under the control of a promoter (P), can be activated by an enhancer (E) when the enhancer is located just upstream of the promoter, within an intron, downstream of the gene or far upstream of the gene.

Figure 2. An active enhancer (E) is correlated with localization of linked genes far from heterochromatin. (a) An enhancer bound by activator and coactivator proteins localizes a gene locus far from heterochromatin, which increases the stability of transcription. (b) The absence of a functional enhancer – when the enhancer is present in a cell type missing the appropriate DNA-binding factors, or is absent or mutated (X) – results in a gene locus located proximal to heterochromatin, where transcription is unstable or silenced (b).

Figure 3. Some proposed mechanisms for enhancer–promoter communication. A distal enhancer (E) may activate transcription by direct interactions with the promoter (P); enhancer–promoter contact may occur by simple diffusion (‘simple looping’), by an active scanning mechanism (‘tracking’), or with the aid of proteins bound to the intervening DNA (‘linking?’). Alternatively, enhancer-mediated gene activation may occur by an indirect mechanism, such as the linking model, in which a chain of protein complexes extends from the enhancer to the promoter and serves as the activation signal (‘linking’). The direct and indirect models are not mutually incompatible: as shown (‘linking and looping’), the role of a chain of protein complexes may be to organize the intervening DNA such that direct interactions can occur.