Modeling of the Genetic Switch of Bacteriophage TP901-1: A Heteromer of CI and MOR Ensures Robust Bistability

The lytic–lysogenic switch of the temperate lactococcal phage TP901-1 is fundamentally different from that of phage lambda. In phage TP901-1, the lytic promoter PL is repressed by CI, whereas repression of the lysogenic promoter PR requires the presence of both of the antagonistic regulator proteins, MOR and CI. We model the central part of the switch and compare the two cases for PR repression: the one where the two regulators interact only on the DNA and the other where the two regulators form a heteromer complex in the cytoplasm prior to DNA binding. The models are analyzed for bistability, and the predicted promoter repression folds are compared to experimental data. We conclude that the experimental data are best reproduced the latter case, where a heteromer complex forms in solution. We further find that CI sequestration by the formation of MOR:CI complexes in cytoplasm makes the genetic switch robust.
Keyword: sequestration,temperate bacteriophage TP901-1,genetic switch,protein interaction,mixed feedback loop