As noted previously, enhancers generally range in length from about 50 to 200 bp and include binding sites for several transcription factors. Analysis of the roughly 50-bp enhancer that regulates expression of β-interferon, an important protein in defense against viral infections in vertebrates, provides a good example of the structure of the DNA-binding domains of several transcription factors bound to the several transcription-factor-binding sites that constitute an enhancer (Figure 9-34). The term enhanceosome has been coined to describe such large DNA-protein complexes that assemble from transcription factors as they bind to the multiple binding sites in an enhancer.

Because of the presence of flexible regions connecting the DNA-binding domains and activation or repression domains in transcription factors (see Figure 9-28), and because of the ability of interacting proteins bound to distant sites to produce loops in the DNA between their binding sites (see Figure 9-5), considerable leeway in the spacing between regulatory elements in transcription-control regions is permissible. This tolerance for variable spacing between binding sites for specific transcription factors, and between promoter binding sites for the general transcription factors and for Pol II, probably contributed to rapid evolution of gene control in eukaryotes. Transposition of DNA sequences and recombination between repeated sequences over evolutionary time probably created new combinations of control elements that were subjected to natural selection and retained if they proved beneficial. The latitude in spacing between regulatory elements probably allowed many more functional combinations to be subjected to this evolutionary experimentation than would be the case if constraints on the spacing between regulatory elements were strict, as for most genes in bacteria.

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