## 12 Spatially Shifting Superhelicity Optimum Determines the Temporal Gene Expression
\begin{table}
\begin{tabular}{c c c c c} \hline \hline \multirow{2}{*}{**Gene Promoter**} & **Distance from** & \multirow{2}{*}{**Condition**} & \multicolumn{2}{c}{**Optimal \({}^{*}\)**} \\  & **OriC (bp)** & & **Superhelical Density (o)** & **\#References** \\ \hline _hisR_ & 62,500 & In vitro & \(-\)\(-\)\(-\)0.08 to \(-\)0.1 & [172] \\ _rmAP1_ & 120,000 & In vitro & \(-\)\(-\)\(-\)\(-\)0.076 & [99] \\ _fis_ & 508,500 & In vitro \& in vivo \& \(-\)\(-\)\(-\)0.07-to \(-\)0.08 & [39] \\ _tyrT_ & 1,967,600 & In vitro & \(-\)\(-\)\(-\)0.05-0.06 & [83] \\ _osmE_ & 2,097,900 & In vitro & \(-\)\(-\)\(-\)0.03-0.04 & [156] \\ \hline \hline \end{tabular} \({}^{*}\)The promoter activity declines on both sides of the indicated \(\sigma\) values.  
\end{table} 
Table 1: Optimal superhelical density for promoter activity as a function of distance from OriC (OriC at 3.92 Mbp; Ter at 1.59 Mbp). Figure 3: The proposed model of the coupling of the temporal gradient of superhelicity with spatial gradient of DNA thermodynamic stability as a device determining the spatiotemporal gene expression. **(A)**. The _E. coli_ genomic wheel with macrodomains depicted on the outer ring: green--Ori; dark blue--left; red--right; black--the left and right non-structured domains; light blue --Ter macrodomain. On the genomic wheel, the distribution of free negative melting energy (-ve fME, inner ring; 500 kb scanning window) is color-coded in blue (for high) and red (for low). The -ve fME was defined using the parameters of Santa Lucia [173]. The positions of OriC and Ter are indicated. (**B**). The horizontal arrow indicates the passage of time after the nutritional shift-up and associated decrease in global DNA negative superhelicity (-ve SC) during the growth cycle. (**C**). The plot showing the temporal variation in different parameters in the gene expression profile obtained during the growth cycle from inoculation of cells (at 0 min) to the late stationary phase [12]. The different curves were normalized (0;1) to compare them in one plot. Expression values of genes responding to high negative supercoiling (_hyp_ genes) and DNA relaxation (_rd_ genes) are normalized to the expression of all genes. Negative melting energy and distance to origin were averaged over all genes weighted by their expression. Because melting energy is by convention expressed as a negative \(\Delta\)G value, high melting energies have a lower (more negative) numerical value, i.e., the lower the negative melting energy value the higher the G/C content. Note that the high negative melting energy values correlate with small distances to replication origin. The envelopes of the curves indicate the standard deviation at 10% random remapping of the expression patterns to genes. The optical density and partial oxygen pressure, respectively, are indicated by the dashed blue and green lines. For growth conditions see legend in Figure 1. Abscissa--time in minutes after inoculation. Ordinate--relative frequency in arbitrary units. (**D**). Temporal changes of ion composition and intracellular pH. IN and OUT indicate the intra- and extracellular compartments. Arrows indicate directional (influx/efflux) changes. The colored dashed lines drawn between the panels (**C**) and (**D**) correlate the growth stages indicated in (**D**) to time intervals in (**C**). For details see the text. We have argued that the process of replication as well as of ribosomal gene transcription proceeding directionally from OriC toward Ter imposes a supercoiling asymmetry with higher negative superhelicity accumulated at the OriC pole of the chromosome [6; 66]. At the early growth stage under conditions of high negative superhelical density, the OriC proximal G/C-rich sequences are likely to be transcribed optimally. However, it is conceivable that the gradual decrease in the global superhelical density during the growth cycle [68] would shift the optimum of the promoter supercoiling response toward genomic regions with lower average G/C content and hence, away from OriC toward Ter.