Image courtesy of Yves Brun.

Caulobacter crescentus is the kind of bacterium it's a pleasure to have around. This single-celled, aquatic organism (which belongs to the same subclass as the less friendly Rickettsia and Agrobacterium) is the most prevalent non-pathogenic bacterium in nutrient-poor freshwater streams and is one of the organisms responsible for sewage treatment and for removing heavy metals from waste water. Its properties make it interesting to study from a developmental point of view. For example, at each cell division, C. crescentus divides into two morphologically distinct daughter cells (shown in the photo): one that resembles the mother (that is, a stalked cell) and a free-swimming cell (a swarmer) that bears a flagellum. C. crescentus is also an ideal system in which to do transcriptional studies. Unlike multicellular organisms, in which gene expression is coordinated by external cues and hormonal signals, the important steps in C. crescentus's life cycle depend entirely on the internal environment, that is, on the relationship between its genes.

Now that the genomic sequence of C. crescentus's single 4-Mb chromosome is complete, post-genomic efforts are underway to understand how the expression profiles of this bug's genes relate to each other. A recent report in Science has shown that the transcription of 19% of C. crescentus's genes (of which there are nearly 3,000) is temporally controlled, and among these are genes that regulate the cell cycle.

Laub and colleagues found that the expression profiles of 553 genes varied in a cyclical pattern during the cell cycle, peaking at discrete times. Among these were genes that had previously been shown to have cell-cycle-related functions. For many of these genes, expression rose just before or coincident with the cell-cycle-related event itself: for example, genes required for nucleotide synthesis were switched on just before the onset of DNA replication. Furthermore, genes whose products were part of a multi-protein complex — the whip-like flagellum, for example — were co-expressed.

The cell cycle can run smoothly only if the timing of each event is precisely coordinated with that of others — an order that is easiest to achieve in the presence of a regulatory hierarchy. CtrA is a critical response regulator whose activity depends on the cell cycle and may be at the top of one such hierarchy. The study showed that the expression of 26% of cell-cycle-regulated genes was affected by a loss-of-function mutation in CtrA. Over a quarter of these genes had promoters with the consensus CtrA binding sites, and are therefore good candidates for direct regulation by CtrA.

This leaves 409 genes still outstanding whose expression is cell-cycle-dependent but that are not influenced by CtrA. Further studies should focus on identifying which master regulatory proteins — there are 27 candidates — account for the periodic expression of these genes.