Figure 1. Sporulation regulatory network in Streptomyces coelicolor.

Previous studies described in the introduction have indicated that the sigma factor whiG (σ^whiG), which orchestrates the transition from aerial hyphal growth to a sporulation-specific program, is expressed in all stages of growth but becomes active only during a short window early in the sporulation process. “σ^whiG” indicates active WhiG; inactive WhiG is in brackets. The transcriptional regulator BldD is required to limit WhiG activity prior to sporulation, although the exact mechanism is not understood. Once active, WhiG directs the transcription of at least two sporulation factors, WhiI and WhiH, which themselves do not become active until later in sporulation. WhiA and the Fe-S cluster protein WhiB mutually regulate each other's expression, and WhiA is also required in vivo to activate its own sporulation-specific transcription. Two other factors—the ParAB and FtsZ genes—are required for hyphal chromosome segregation and septation, respectively. WhiA has been shown in vivo to be required for the sporulation-specific expression of both ParAB and FtsZ. Other sporulation factors required for the subsequent spore maturation include WhiD, WhiE and σ^F. As described in this paper and indicated with grey lines in the figure, WhiA physically binds to its own promoter and to the Parp₂ promoter (i.e. sporulation-specific), consistent with a role in gene activation, and also binds to WhiG. WhiG activates expression of WhiA. A model consistent with those findings is that when WhiA accumulates, it binds to and inhibits WhiG activity, thereby forming a feedback loop that contributes to the inactivation of WhiG and itself. Other factors may also be required to fully limit WhiG activity.