Figure 6.

The use of 'inhibit' and 'activate' arrows to represent steric hindrance and cooperative binding reactions in a model of the lysis-lysogeny decision network of phage lambda [15]. A single-molecule icon is used to represent transcription factors that are actually homodimers of CI, Cro and CII. Key pathways for the synthesis and degradation of CI and Cro are as follows. Binding of RNA polymerase (RNAP) to the PRM promoter activates production of CI via the cI gene. The binding of 'RNAP' (the quotation marks signify that the icon is a duplicate of the RNAP icon and is not a separate entity) to promoter PR activates production of cro RNA via the cro gene. Binding of CII to promoter PRE at the opposite end of the cro gene activates production of antisense cro RNA ('anti-cro'). cro RNA required to produce Cro protein is degraded and removed from the system by a quenching reaction with anti-cro. The degradation of CI (the vertical reaction arrow at the top of the CI icon) depends on the proteolytic enzyme RecA, which is activated by ultraviolet light (UV). Cro degradation is unregulated, and CII degradation is not represented. The diagram is laid out to emphasize the symmetry between the CI and Cro synthesis and degradation pathways. The symmetry is broken, however, when one considers how competitive binding of the transcription factors (CI and Cro) to the operators (OR1, OR2 and OR3) controls access of RNA polymerase to the back-to-back promoters PRM and PR. Transcription repression by CI and Cro is nearly symmetric as they each limit access (by steric hindrance; shown as double-headed 'inhibit' arrows) of RNA polymerase to the promoters. RNA polymerase access to PR is limited in four instances by CI or Cro binding to either OR1 or OR2, whereas access to PRM is limited in three instances by Cro binding to either OR2 or OR3, or by CI binding to OR3. The break in symmetry occurs because, rather than being repressive, CI binding to OR2 actually enhances PRM transcription, which is stabilized in two ways. First, CI bound to OR3 directly binds RNA polymerase to stabilize its binding at its promoter site. Second, CI stabilizes its own binding to OR2 by establishing a homodimerization bond (the dimerization arrow extending to the right of the CI icon) with a CI molecule bound to OR1. The result is two trimers (CI-gene-RNAP and CI-gene-CI) within which the ability of pairs of bonds to stabilize a third bond is indicated by a double-tailed activation arrow. As such bond stabilization is mutually cooperative, the three double-tailed arrows are superimposed to form the triadic arrows shown in the figure.