FIGURE 9-4 Regulation of transcription from the lac operon of E. coli. (Top) The transcription-control region, composed of roughly a hundred base pairs, includes three protein-binding regions: the CAP site, which binds catabolite activator protein; the lac promoter, which binds the σ⁷⁰-RNA polymerase complex; and the lac operator, which binds lac repressor. The lacZ gene encoding the enzyme β-galactosidase, the first of the three genes in the operon, is shown to the right. (a) In the absence of lactose, very little lac mRNA is produced because the lac repressor binds to the operator, inhibiting transcription initiation by σ⁷⁰-RNA polymerase. (b) In the presence of glucose and lactose, lac repressor binds lactose and dissociates from the operator, allowing σ⁷⁰-RNA polymerase to initiate transcription at a low rate. (c) Maximal transcription of the lac operon occurs in the presence of lactose and the absence of glucose. In this situation, cAMP increases in response to the low glucose concentration and forms a CAP-cAMP complex, which binds to the CAP site, where it interacts with RNA polymerase to increase the rate of transcription initiation. (d) The tetrameric lac repressor binds to the primary lac operator (O1) and one of two secondary operators (O2 or O3) simultaneously. The two structures are in equilibrium. See B. Muller-Hill, 1998, Curr. Opin. Microbiol. 1:145.

[Part (d) data from M. Lewis et al., 1996, Science 271:1247-1254, PDB IDs 1lbh and 1lbg; and R. Daber et al., 2007, J. Mol. Biol. 370:609-619, PDB ID 2pe5.]