Figure 3.
Pap phase variation model. A model for the transition from phase OFF to phase ON is shown in panels A–F. In A, the OFF state is shown in which Lrp binds to sites 1–3, blocking methylation of GATCprox and inhibiting papBA transcription. Nonmethylated pap GATC sites are depicted as open circles, and methylated sites are depicted as closed circles. The binding of Lrp at sites 1–3 reduces the affinity of Lrp for sites 4–6 (“mutual exclusion,” see Fig. 5), and is depicted by an arrow with a negative sign. Transition to the phase ON state is hypothesized to require DNA replication, which dissociates Lrp from pap DNA generating two daughter duplexes of which one is shown (B). PapI and Dam work together to increase the affinity of Lrp for sites 4–6 as discussed in the paper (C). Activation of pap transcription requires cAMP-CAP (D), which stimulates PapB transcription (E). Because PapB activates papI transcription, the phase ON state is self-perpetuating (F).