A monomer of a typical transcription regulator recognizes about 6–8 nucleotide pairs of DNA. However, sequence-specific DNA-binding proteins do not bind tightly to a single DNA sequence and reject all others; rather, they recognize a range of closely related sequences, with the affinity of the protein for the DNA varying according to how closely the DNA matches the optimal sequence. Hence, cis-regulatory sequences are often depicted as “logos” which display the range of sequences recognized by a particular transcription regulator (Figure 7–9A and B). In Chapter 6, we saw this same representation at work for the binding of RNA polymerase to promoters (see Figure 6–12).
The DNA sequence recognized by a monomer does not contain sufficient information to be picked out from the background of such sequences that would occur at random all over the genome. For example, an exact six-nucleotide DNA sequence would be expected to occur by chance approximately once every 4096 nucleotides (46), and the range of six-nucleotide sequences described by a typical logo would be expected to occur by chance much more often, perhaps every 1000 nucleotides. Clearly, for a bacterial genome of 4.6 × 106 nucleotide pairs, not to mention a mammalian genome of 3 × 109 nucleotide pairs, this is insufficient information to accurately control the transcription of individual genes. Additional contributions to DNA-binding specificity must therefore be present. Many transcription regulators form dimers, with both monomers making nearly identical contacts with DNA (Figure 7–9C). This arrangement doubles the length of the cis-regulatory sequence recognized and greatly increases both the affinity and the specificity of transcription regulator binding. Because the DNA sequence