The lactose operon-controlling elements: a complex paradigm.

The lactose-controlling elements have been considered to be the simple paradigm of a cis-acting genetic regulatory system, containing a promoter whose activity is modulated by an operator and a catabolite gene activator protein (CAP)-binding site. The reality is considerably more complex. We now know that transcription is negatively regulated as a result of the repressor binding to three binding sites: the operator, a secondary repressor-binding site within the lacZ gene and a tertiary repressor-binding site upstream near lacI. In addition to the promoter, the lac-controlling elements contain five promoter-like elements. The physiological role, if any, of these promoter-like elements is not clear, although three of them can be activated by single base pair changes to give high levels of in vivo expression. Finally, the positive activator protein CAP has been found to bind to a secondary site which is coincident with the operator. No role has been identified for this secondary CAP-DNA complex.