Abstract
The coordination of bacterial genomic transcription involves an intricate network of interdependent genes encoding nucleoid-associated proteins (NAPs), DNA topoisomerases, RNA polymerase subunits and modulators of transcription machinery. The central element of this homeostatic regulatory system, integrating the information on cellular physiological state and producing a corresponding transcriptional response, is the multi-subunit RNA polymerase (RNAP) holoenzyme. In this review article, we argue that recent observations revealing DNA topoisomerases and metabolic enzymes associated with RNAP supramolecular complex support the notion of structural coupling between transcription machinery, DNA topology and cellular metabolism as a fundamental device coordinating the spatiotemporal genomic transcription. We analyse the impacts of various combinations of RNAP holoenzymes and global transcriptional regulators such as abundant NAPs, on genomic transcription from this viewpoint, monitoring the spatiotemporal patterns of couplons—overlapping subsets of the regulons of NAPs and RNAP sigma factors. We show that the temporal expression of regulons is by and large, correlated with that of cognate regulatory genes, whereas both the spatial organization and temporal expression of couplons is distinctly impacted by the regulons of NAPs and sigma factors. We propose that the coordination of the growth phase-dependent concentration gradients of global regulators with chromosome configurational dynamics determines the spatiotemporal patterns of genomic expression.
Highlights
The bacterial transcriptional regulation system is one of the most fascinating of evolutionary devices
We observe positive correlation between the temporal expression of global regulatory genes and their cognate regulons as well as between the regulons and couplons on the one hand, and positive correlations between the spatial organization of regulons and couplons on the other. These observations suggest that the expression of global regulators is coordinated with organization of target genes in the chromosome, lending support to the hypothesis that transcriptional regulation shapes the spatial organization of genes [104,130]
The determinative impact of the regulons of nucleoid-associated proteins (NAPs) and global transcription factors (TFs) on spatial patterns of cognate RpoD couplons is apparently related to the fact that RpoD transcribes vast majority of the genes and so, tends to impose uniformity, whereas the effects of NAPs and global TFs regulating subsets of genes convey discreteness to the spatial couplon patterns (Figure 5A,C; Supplementary Figures S3 and S4)
Summary
The bacterial transcriptional regulation system is one of the most fascinating of evolutionary devices. The main hallmark of this system ( a stumbling block for exploring it) is its organizational complexity, featuring control mechanisms involving spatiotemporally coordinated communications between its analog and digital components [5,6] In this system, the unique sequences of individual genes represent discontinuous (i.e., digital) entities expressed as continuous (analog) variables—different species of indistinguishable protein molecules produced at various concentrations, including the abundant DNA binding proteins. The nature of the regulation of the genes that are not part of the TRN remained uncertain until the development of high-throughput approaches, which discovered distinct genome-wide patterns of transcriptional responses to changes of the chromosomal DNA topology induced by DNA topoisomerase inhibitors and environmental stress [13,14,15,16,17] This latter type of genetic control, mediated by a continuous variable—namely, the concerted alterations of DNA superhelical density and composition of abundant chromatin architectural proteins—was dubbed analog control. It is the synthesis of this ordering that impacts the overall pattern of bacterial gene regulation
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