As noted earlier, transcription from many eukaryotic promoters can be stimulated by control elements located thousands of base pairs away from the transcription start site. Such long-distance transcription-control elements, referred to as enhancers, are common in eukaryotic genomes but fairly rare in bacterial genomes. Procedures such as linker scanning mutagenesis have indicated that enhancers, usually on the order of 200 bp long, are, like promoter-proximal elements, composed of several functional sequence elements of about 6–10 bp each. As discussed later, each of these regulatory elements is a binding site for a sequence-specific DNA-binding transcription factor.

Analyses of many different metazoan enhancers have shown that they can occur with equal probability upstream from a promoter or downstream from a promoter within an intron, or even downstream from the final exon of a gene, as in the case of the SALL1 gene (see Figure 9-10a). Many enhancers are cell-type-specific. For example, an enhancer controlling Pax6 expression in the retina was characterized in the intron between exons 4 and 5 (see Figure 9-9a), whereas an enhancer controlling Pax6 expression in the hormone-secreting cells of the pancreas is located in a roughly 200-bp region upstream of exon 0 (so named because it was discovered after the exon called “exon 1”).