Coordinated regulation of gene expression by E ... - Jacobs University

CONCLUSION
5 Conclusion
Regulation of cellular growth involves coordinated gene expression programs. An
essential question is, how during growth the global transcription is organized in the
genome. We demonstrate in unicellular organism E.coli that the coordination of growth
phase-dependent transcription involves spatiotemporal organization of supercoiling
sensitivity in the genome. On the example of tyrT promoter we demonstrate how the
sequence organization of a promoter can determine supercoiling sensitivity. We show
that the distributions of supercoiling sensitivity are modulated by chromatin proteins -
both at global and local promoter levels - involved in organizing cellular metabolism
during successive stages of growth. More compellingly, our approach identifies a tight
coupling between unique genes and the ubiquitous torsional properties of the genomic
DNA in coordinating essential metabolic functions. Global regulation thus appears to
act as a genuine device converting the “analog” information of torsional energy
distributions into “digital” patterns of genomic activity (and vice versa). This work thus
not only validates the John von Neumann notion on the coordination of genetic
information at a most basic level, but also offers a novel strategy for further
investigations. Notably, it is now evident that DNA supercoiling plays an increasingly
important role in regulation of eukaryotic transcription [Dunaway & Ostrander, 1993],
suggesting that this type of approach may facilitate the understanding of fundamental
mechanisms coordinating the gene expression.
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