Coordination of cell decisions and promotion of phenotypic diversity in B. subtilis via pulsed behavior of the phosphorelay

The phosphorelay of Bacillus subtilis, a kinase cascade that activates master regulator Spo0A ∼ P in response to starvation signals, is the core of a large network controlling the cell's decision to differentiate into sporulation and other phenotypes. This article reviews recent advances in understanding the origins and purposes of the complex dynamical behavior of the phosphorelay, which pulses with peaks of activity coordinated with the cell cycle. The transient imbalance in the expression of two critical genes caused by their strategic placement at opposing ends of the chromosome proved to be the key for this pulsed behavior. Feedback control loops in the phosphorelay use these pulses to implement a timer mechanism, which creates several windows of opportunity for phenotypic transitions over multiple generations. This strategy allows the cell to coordinate multiple differentiation programs in a decision process that fosters phenotypic diversity and adapts to current conditions.

The phosphorelay of Bacillus subtilis controls differentiation into sporulation and other phenotypes in response to starvation. This kinase cascade pulses with peaks of activity coordinated with the cell cycle. We review the role of this complex dynamical behavior in timing cell fate decisions and generating phenotypic diversity at the colony level.

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