7. Repression can occur at multiple loci

10.7 Repression can occur at multiple loci

Key terms defined in this section

Autogenous control describes the action of a gene product that either inhibits (negative autogenous control) or activates (positive autogenous control) expression of the gene coding for it.

The lac repressor acts only on the operator of the lacZYA cluster. However, some repressors control dispersed structural genes by binding at more than one operator. An example is the trp repressor, which controls three unlinked sets of genes:

• An operator at the cluster of structural genes trpEDBCA controls coordinate synthesis of the enzymes that synthesize tryptophan from chorismic acid.
  
• An operator at another locus controls the aroH gene, which codes for one of the three enzymes that catalyze the initial reaction in the common pathway of aromatic amino acid biosynthesis.
  
• The trpR regulator gene is repressed by its own product, the trp repressor. So the repressor protein acts to reduce its own synthesis. This circuit is an example of autogenous control. Such circuits are quite common in regulatory genes, and may be either negative or positive. (We discuss examples later in this chapter and in 11 Phage strategies.)

Figure 10.19 The trp repressor recognizes operators at three loci. Conserved bases are shown in red. The location of the mRNA varies, as indicated by the red arrows.

A related 21 bp operator sequence is present at each of the three loci at which the trp repressor acts. The conservation of sequence is indicated in Figure 10.19. Each operator contains appreciable (but not identical) dyad symmetry. The features conserved at all three operators include the important points of contact for trp repressor. This explains how one repressor protein acts on several loci: each locus has a copy of a specific DNA-binding sequence recognized by the repressor (just as each promoter shares consensus sequences with other promoters).

Figure 10.20 Operators may lie at various positions relative to the promoter.

Figure 10.20 summarizes the variety of relationships between operators and promoters. A notable feature of the dispersed operators recognized by TrpR is their presence at different locations within the promoter in each locus. In trpR the operator lies between positions -12 and +9, while in the trp operon it occupies positions -23 to -3, but in the aroH locus it lies farther upstream, between -49 and -29. In other cases, the operator lies downstream from the promoter (as in lac), or apparently just upstream of the promoter (as in gal, where the nature of the repressive effect is not quite clear). The ability of the repressors to act at operators whose positions are different in each target promoter suggests that there could be differences in the exact mode of repression, the common feature being that RNA polymerase is prevented from initiating transcription at the promoter.