SpoOA, a transcriptional activator protein in Bacillus subtilis, is a well-established central player in sporulation. Now, a new study, published in Genes and Development, provides compelling evidence that SpoOA, rather than simply controlling the initiation of sporulation, is predominantly a cell-specific transcriptional regulator.

B. subtilis is a well-characterized model system for differentiation and programmed cell-specific gene expression. During sporulation in Bacillus, two cell-types form: the mother cell and the forespore, which is destined to become a spore. Without the SpoOA response-regulator, sporulation doesn't occur.

A complex phosphorelay integrates metabolic, environmental and cell-cycle cues to activate SpoOA. Phosphorylated SpoOA activates the transcription of sporulation genes, which tips the balance so that sporulation occurs. So, as in eukaryotes, phosphorylation of key proteins regulates cell-cycle progression.

However, Fujita and Losick noticed that an operon in the mother cell controlled by SpoOA was transcribed after sporulation had initiated, so they investigated whether SpoOA controls gene expression following sporulation initiation. Surprisingly, SpoOA was shown to be active throughout sporulation. Furthermore, it was active in a cell-specific fashion. SpoOA accumulated in the mother cell, and overexpression of a constitutively active SpoOA mutant in the forespore drastically reduced sporulation efficiency. Finally, expression, in the mother cell, of a truncated form of SpoOA, which competed with native SpoOA for phosphorylation, reduced sporulation efficiency. So, the location and activity of SpoOA is crucially important for development. Viewed in this light, SpoOA is analogous to the related transcription factor CtrA in Caulobacter crescentus. Like SpoOA, CtrA is a master regulator that becomes a cell-specific transcription factor during the cell cycle of Caulobacter. CtrA activates or represses the expression of one-quarter of the Caulobacter cell-cycle-regulated genes, integrating DNA replication, morphogenesis and cell division. Caulobacter divides to produce two cell types: a stalked cell and a swarmer cell, which is a dispersal cell that swims until conditions allow renewed cell division.

CtrA binds to, and silences, the origin of replication in swarmer cells — initiation of chromosome replication depends on temporally controlled proteolysis of CtrA in the stalked cell. Why is SpoOA activity restricted to one cell type? When the wall is synthesized between mother cell and forespore, two-thirds of the forespore chromosome remains in the mother cell. As the excluded chromosome is pumped into the forespore, certain genes are asymmetrically expressed. So, asymmetric expression of phosphorelay genes might result in SpoOA phosphorylation only in the mother cell. This could ultimately decide the fate of SpoOA, through targeted proteolysis of unphosphorylated SpoOA in the forespore. Comparisons between the parallel systems in Caulobacter and Bacillus will undoubtedly push forward our understanding of programmed cell-specific gene expression.