Global transcriptional optimization in microorganisms

François Képès

Chromosome configuration, genome organization and genome function may be expected to be interdependent. Studies by several teams have emphasized periodic positioning of microbial genes that are either co-regulated, co-expressed, evolutionarily correlated, or highly codon-biased. On the basis of our first results, we have postulated in 2003 the existence of a positive feedback loop connecting a periodic genome organization to chromosome configuration on to genome function / expression. Indeed, we recently showed with a thermodynamic model that a periodic relative gene positioning is crucial to achieve solenoidal chromosome configurations that result in the specific clustering of co-functional genes into transcription factories. In turn, the resulting chromosome configuration improves the overall dynamics of genome function, e.g. transcriptional control, by elevating the local concentrations of the interacting biomolecules. Finally, this improved dynamics of genome function augments the force that allows specific genome organizations to affect chromosome folding. This last point may be thought of as the analog for mRNA of the well-established case of stable RNA in the eukaryotic nucleolus or prokaryotic pseudo-nucleolus.

The picture that emerges from these studies is one of a collective transcriptional scheme acting in a microbial cell, that globally optimizes the intensity of each transcriptional regulation. This collective transcriptional scheme suggests ways to design coordinated regulatory effects at the scale of a genome.