## 11 Genomic Transcription during the Bacterial Growth Cycle Is Steered by Supercoil Energy  
Changes in DNA supercoiling are assumed to mediate the transmission of environmental changes to the chromosome, responding not only to the altered availability of metabolic resources during the growth cycle [68] but also to the various stress factors including suboptimal oxygen tension, temperature, and osmolarity [152; 153; 154; 155]. This mediation by supercoiling is due to the capacity of the DNA double helix to sense the environmental conditions and to respond by adjusting accordingly the superhelical density on the one hand, and by channeling the available superhelical energy into corresponding gene expression patterns on the other. We have argued that during the bacterial growth cycle, changes in DNA topology modulate the binding of DNA architectural proteins and the activity of transcription machinery concertedly, resulting in orchestrated directional alterations of chromatin architecture and gene expression. Several lines of evidence are consistent with this notion. First, the continuous alteration of DNA superhelical density during the growth cycle is dependent on the availability of nutritional resources [68]. As in the progression of the population along the growth cycle, the superhelical density decreases, the tightness of apical loops and DNA interwindings also decreases, and so the accessibility to the RNA polymerase changes. As mentioned above, from the early exponential phase to the early stationary phase dominated by the RNAPoS\({}^{70}\) holoenzyme, the number of total superhelical turns per 1 kb would reduce from ~8 to ~3, with a reduction in unconstrained turns likely to be greater and hence, the available DNA superhelical torque lower. Under these conditions, the RNAPoS\({}^{5}\) holoenzyme preferring relaxed DNA substrates for transcription becomes active [25; 134]. At the early growth stage the RpoZ-dependent stabilization of the RNAPoS\({}^{70}\) holoenzyme facilitates the utilization of negatively supercoiled templates, whereas the lack of RpoZ leads to a global DNA relaxation and an increased activity of the RNAPoS\({}^{5}\) holoenzyme, switching the global transcription preferences to the utilization of the relaxed DNA templates [155]. Importantly, the impact of accumulated \(\sigma^{S}\) could not be detected until the superhelical density of the reporter plasmids subsided to relatively low levels (\(\Delta\)Lk of \(\sim\)3-4 between the late exponential phase and the early stationary phase, where the \(\sigma^{S}\) impact was observed). It was thus inferred that the variations in DNA supercoiling as a function of the growth phase act as a checkpoint, precluding the shift from the RNAP\(\sigma^{70}\) to the RNAP\(\sigma^{S}\) transcriptional machinery until the growth conditions become unfavorable enough to cause entry into the stationary phase [156]. Second, the superhelical density and the supercoiling response of the genomic transcription change coordinately both during the growth cycle of _E. coli_[31] and during the circadian cycle of gene expression in cyanobacteria. A combination of topological analyses with transcriptomics data in _Synechococcus elongatus_ suggested that each topological state corresponded to a unique state of gene expression, indicating that supercoiling plays a primary role in regulating circadian gene expression [157]. Notably, the DNA sequence characteristics of genes monotonically activated and repressed by chromosomal relaxation during the circadian cycle were similar to those of the supercoiling-responsive genes in _E. coli_. Third, the sequential activation of sets of primary and downstream regulatory genes was observed in response to the long-term supercoiling imbalance achieved by modulating the _topA_ gene expression in _Streptomyces coelicolor_, whereby increased negative superhelicity modified the levels of topoisomerases and NAPs coordinately [40].