Figure 2.

Stochastic switching in the lac bistable gene network. (A) Under maintenance conditions, the lac operon is OFF when the lac repressor is bound to the lac operator (indicated by the solid red line) and the inducer thio-methylgalactoside (TMG) remains extracellular; stochastic events that lead to a transient derepression of the lac operon will result in a burst of lac operon functions and the appearance of permease will initiate an autocatalytic positive-feedback response (indicated by solid blue lines), which will heritably maintain the ON state (TMG induces an allosteric transition in lac repressor, indicated by the dashed red line, so that it no longer binds to the lac operator), and the cell will exhibit green fluorescence. (B) Wild-type (CH458) and ΔmutT (CH505) cells that were originally ON or OFF were sub-cultured and grown in media containing various concentrations of TMG. Each value is the average ±SD from four independent cultures. The shaded area highlights the maintenance concentration of 6-μM TMG for these strains. (C) OFF wild-type cells (red histograms) and OFF ΔmutT cells (blue histograms) were diluted and grown in media containing 6-μM TMG. After 42 h growth, flow cytometry was performed to determine the frequency of epigenetically ON cells in 49 independent cultures of each strain; the ΔmutT histograms are superimposed over the wild-type histograms (10⁴ cells interrogated for each histogram). (D) The ΔmutT epigenetic-switch frequency is not significantly increased over the wild-type value (Mann–Whitney Rank Sum Test, P = 0.13).