Control of gene expression in prokaryotes: the lac operon model

In the presence of lactose, E.coli bacteria are able to initiate the production of galactosidase permease, a membrane transport protein able to traffic high levels of lactose across the cellular membrane, as well as $\beta$‍-galactosidase, an enzyme that cleaves lactose into glucose and galactose. In order to understand the mechanistic basis for the selective expression of lactose-processing genes, researchers created three different E.coli lines, each with mutations affecting their ability to process lactose. They then cultured each of the three lines in either lactose-only media or glucose-only media, and monitored intracellular accumulation of lactose and $\beta$‍-galactosidase activity.

Table 1. Phenotypic observations for three different E.coli mutants when cultured in lactose-containing media (no glucose). Note: $\beta$‍-galactosidase activity was assayed using an indicator molecule other than lactose.

Table 2. Phenotypic observations for three different E. coli mutants when cultured in glucose-containing media (no lactose). Note: $\beta$‍-galactosidase activity was assayed using an indicator molecule other than lactose.

Based on data similar to that presented in the above two tables, François Jacob, Jacques Monod, and collaborators advanced a set of hypotheses that have come to being known as the lac operon model of gene regulation in prokaryotes. An operon is defined as a group of regulatory elements and the genes that the elements control, which are transcribed as one mRNA molecule. The Jacob-Monod group hypothesized that an operon in E. coli, the lac operon, accounts for the lactose processing behavior observed in the above data. According to this model, the lac operon itself consists of two genes: lacZ, which codes for $\beta$‍-galactosidase, and lacY, which codes for galactosidase permease (the model also contains a gene called lacA, not discussed here). Crucially, the model also hypothesizes that the transcription of the lac operon is controlled by the LacI gene, which codes for a DNA-binding repressor protein. This repressor protein down-regulates the transcription of the lac operon by binding immediately upstream of lacZ and lacY, at a site called the operator, which serves to impede the progress of RNA polymerase. Extracellular lactose has the ability to enter the cell and bind the repressor protein, altering its conformation in such a way that it releases from the operator, allowing for unimpeded transcription of the lac operon.