In negative control, transcription is decreased in the presence of a repressor protein. E. coli can also use positive control to increase transcription through the presence of an activator protein. For an example we return to the lac operon, where the relative levels of glucose and lactose determine the amount of transcription. We have seen that in the presence of lactose the lac repressor is unable to bind to the lac operator to repress transcription (see Figure 16.5B). But glucose is the preferred source of energy for the cell, so if glucose and lactose levels are both high, the lac operon is still not transcribed efficiently. This is because efficient transcription of the lac operon requires binding of an activator protein to its promoter.

Low levels of glucose in the cell set off a signaling pathway that leads to increased levels of the second messenger cyclic AMP (cAMP) (see Key Concept 7.3). Cyclic AMP binds to an activator protein called cAMP receptor protein (CRP), producing a conformational change in CRP that allows it to bind to the lac promoter. CRP is an activator of transcription, because its binding results in more efficient binding of RNA polymerase to the promoter, and thus increased transcription of the structural genes (Figure 16.6). In the presence of abundant glucose, cAMP levels are low, CRP does not bind to the promoter, and the efficiency of transcription of the lac operon is reduced. This is an example of catabolite repression, a system of gene regulation in which the presence of the preferred energy source represses other catabolic pathways. The mechanisms controlling positive and negative regulation of the lac operon are summarized in Table 16.1.

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