Multiple regulation of the galactose operon-genetic evidence for a distinct site in the galactose operon that responds to capR gene regulation in Escherichia coli K-12.

Previous results demonstrated that the capR (lon) locus, which is not linked to the gal operon, independently controls the synthesis of the gal operon enzymes and gal mRNA, i.e., galO(+)capR9 strains are derepressed 4- to 6-fold as compared to galO(+)capR(+) strains. A mutation has been isolated and localized in the galactose operator region that defines a new and distinct site of control. Mutation in this site, designated galO(capR+), causes a 4-fold increase in the galactose enzymes, galactokinase (EC 2.7.1.6) and UDP-galactose-4-epimerase (EC 5.1.3.2), in a capR(+) background. These mutants exhibit a reduced response to regulation by the unlinked regulator gene capR (lon). However, the galO(capR+) mutants are still subject to control by the galR repressor, since they can be further derepressed by growth in the presence of D-fucose. They also synthesize more galactokinase when grown in glycerol as compared to glucose. Thus there are now at least three, and probably four, sites for control of mRNA synthesis in the operator-promoter regions of the gal operon, making it one of the most complex control systems to date for a single operon in bacteria. The complexity is sufficient to accommodate models for differentiation in higher organisms that require more than one "switch" to control a single group of genes.