## 9 Role for Changing Chromosome Configuration in Organizing Genomic Transcription
Increased negative superhelicity both facilitates replication initiation and strongly activates the OriC-proximal _fis_ gene expression [37; 39; 129], whereas the accumulation of FIS in turn maintains activated ribosomal RNA transcription [130]. Structurally, the increase in negative superhelicity leads to a branching of plectonemically coiled DNA, thus multiplying the tightly bent apical loops and facilitating the wrapping of DNA by the RNAP \(\sigma^{70}\) holoenzyme [88; 131; 132; 133], which prefers highly supercoiled templates for transcription [134]. Notably, the RNAP \(\sigma^{70}\) holoenzyme demonstrates an OriC-Ter gradient of binding site frequency distribution correlating with that of the gyrase binding sites [6]. Concomitantly with activation of the _fis_ gene, the expression of the _rpoZ_ gene encoding the RpoZ (\(\omega\))subunit of RNA polymerase is also strongly increased [3; 124]. RpoZ stabilizes the polymerase \(\sigma^{70}\) holoenzyme assembly [135] and is also directly involved in mediating the response to ppGpp [23; 136]. FIS activates the _hupA_ gene [137] such that at the early growth stage, the high levels of negative superhelicity and the RNAP \(\sigma^{70}\) holoenzyme coexist with increased levels of the two major \"early\" NAPs--FIS and HU\(\alpha\). High FIS levels boost rRNA synthesis, whereas HU supports the organization of rRNA operons in \"transcription factories\" engaging hundreds of RNAP molecules [66; 138]. The latter effect requires high levels of negative superhelicity [121]. Accordingly, both FIS and HU stabilize negative supercoils [43; 139; 140]. On transition to the stationary phase associated with a shortage of resources, the rapid increase in ppGpp levels (ppGpp spike) decreases both rRNA transcription and the supercoil density around OriC, thus precluding replication initiation [141]. The \(gyrA/B\) gene expression and the gyrase levels subside [123] and the total superhelicity drops to \(\sigma\)--0.03. The down-regulation of the chromosomal OriC pole at this stage is likely supported by the binding of the global repressor H-NS and the \"late\" NAPs such as Lrp and Dps [6; 142], whereas the activation of the Ter pole is attributable to the accumulation of the RNAPoS\({}^{5}\) holoenzyme and IHF, the binding sites for both of which are strongly enriched around the chromosomal Ter pole [6]. Notably, the \"late\" NAPs as well as the RNAPoS\({}^{5}\) holoenzyme, preferentially bind relaxed DNA [3]. Thus, in the stationary phase, the RNAPoS\({}^{5}\) holoenzyme responsible for the maintenance function predominates, whereas the globally relaxed DNA is organized by the binding effects of three abundant NAPs including IHF, which stabilizes planar bends without the substantial constraints of negative superhelicity, Lrp, which constrains positive supercoils, and Dps, which packages the relaxed DNA in a protective crystalline lattice [115; 143]. What happens to the nucleoids of cells enriched for these abundant stationary-phase NAPs on nutritional shift-up? After nutritional shift-up, the compaction state of the nucleoid undergoes marked alterations adopting a more open conformation [144], presumably due to competition between the early and late growth stage NAPs, respectively, FIS and Dps [142; 145]. The DNA binding of IHF and Dps was shown to depend on environmental factors [146]. Under conditions of the increase in DNA negative superhelicity after nutritional shift-up, both IHF and Dps likely start to dissociate from genomic binding sites, perhaps accelerated in part by \"facilitated dissociation\"--a general mechanism thought to modulate gene expression by assisting in the local removal of DNA binding proteins from cognate sites [147; 148; 149]. However, IHF remains stably bound at the chromosomal origin of replication, its dissociation being prevented by the replication initiator protein DnaA cooperating with IHF in initiating chromosomal replication [150]. This latter process is facilitated by FIS protein produced at high levels on nutritional shift-up [151].