Sequences of Controlling Regions of the Lactose Operon
The control region of the lactose operon of E. coli provides an unusually appropriate DNA segment for sequence analysis. Here lie the sites at which the RNA polymerase and the catabolite activator protein act to potentiate synthesis of lac mRNA and the site at which the lac repressor acts to control mRNA synthesis. The repressor protein, a 150,000-dalton tetramer of identical subunits, discerns a unique, short region of DNA among the six million nucleotide sequences on the E. coli genome. The site at which the repressor acts, named the operator by Jacob and Monod (1961), is defined genetically as the locus of mutations that render the adjacent structural genes less sensitive to repressor control: these are cis-dominant constitutive mutations (oc for “operator constitutive”). After the isolation of repressors and the demonstration that these proteins bind to specific sites on DNA (Gilbert and Müller-Hill, 1966; Ptashne, 1967a) and that operator constitutive...