## 7 Transcription Regulation: How RNA Polymerase Communicates with Transcription Factors  
Binding of alternative \(\upsigma\) factors to the RNAP core enzyme is regulated by anti-\(\upsigma\) factor, which forms a stable complex with its target \(\upsigma\) factor and blocks core RNAP binding. Structures of the \(\upsigma\)/anti-\(\upsigma\) factor complex have shown various ways that the core enzyme-binding interface of \(\upsigma\) factor can be masked (Table 2 and Figure 2b). The \(\upsigma\)/anti-\(\upsigma\) complex has also contributed to providing high-resolution images of \(\upsigma\) factor, since \(\upsigma\) factor is notorious for having a heterogenous conformation and is difficult to crystallize in isolation. Bacterial RNAP physically interacts with protein factors during gene regulation. Most bacterial transcription factors bind upstream of promoter DNA and recruit RNAP to target promoters and/or facilitate formation of the open complex. Three crystal structures of a transcription factor, RNAP domain, \begin{table}
\begin{tabular}{l l l l} \hline
**Structure** & **PDB** & **References** & **Source** \\ \hline Phage factor complex & & & \\ \hline Holoenzyme–gp2 & 4 LK0\({}^{\text{\text{\tiny X}}}\), 4 LLG\({}^{\text{\text{\tiny X}}}\) & [36] & A \\ \(\upbeta\) subunit jaw domain–gp2 & 2 LMC\({}^{\text{\text{\tiny N}}}\) & [70] & A \\ \(\upbeta\) subunit flap domain–gp33 & 3 TBI\({}^{\text{\text{\tiny X}}}\) & [71] & A \\ Holoenzyme–gp39 & 3 WOD\({}^{\text{\text{\tiny X}}}\) & [72] & B \\ \(\upbeta\) subunit flap domain –gp39 & 3 WOF\({}^{\text{\text{\tiny X}}}\), 3 WOE\({}^{\text{\text{\tiny X}}}\) & [72] & B \\ \(\upsigma\)\({}^{\text{\text{\tiny 70}}}\) domain4–AsiA & 1 TLH\({}^{\text{\text{\tiny N}}}\) & [17] & A, a \\ \(\upsigma\)\({}^{\text{\text{\tiny A}}}\) domain4–gp67 & 4G8X\({}^{\text{\text{\tiny X}}}\) & [73] & K, a \\ \hline \end{tabular} A: _Escherichia coli_; B: _Thermus aquatics/Thermus thermophilus_; C: _Bacillus subtilis/Bacillus stearothermophilus_; D: _Aquifex aeolicus_; H: _Yersinia pseudotuberculosis_; I: _Mycobacterium tuberculosis_; K: _Staphylococcus aureus_; a: group I \(\upsigma\) factor; b: group II \(\upsigma\) factor; c: extracytoplasmic function (ECF) \(\upsigma\) factor; x: X-ray crystallography method; c: Cryo-EM single-particle analysis method; N: NMR method.  
\end{table} 
Table 2: _Cont._and DNA ternary complex have provided insights into how these factors influence transcription activation through different mechanisms (Table 2 and Figure 2a). Catabolite activator protein (CAP) (also known as cAMP receptor protein CRP) is the most well characterized bacterial transcription factor, providing insights into the interaction between the helix-turn-helix motif and DNA, the allosteric control of DNA binding, and transcription activation. In classical lactose operon regulation [78], CAP binds DNA \(\sim\)60 bp upstream from the transcription start site (class I transcription factor binding site) and interacts with \(\alpha\)CTD [6, 79]. The crystal structure of the CAP-\(\alpha\)CTD-DNA ternary complex provided a first view of the transcription factor-RNAP interaction as well as the \(\alpha\)CTD-DNA interaction (PDB: 1 LB2) [61]. The structure showed that these proteins interact with small interfaces, but it is sufficient for RNAP to target the promoter. A low-resolution view of the transcription initiation complex including _E. coli_ RNAP, CAP, and promoter DNA has been determined by cryo-electron microscopy (EMD ID, EMD-5127; PDB: 3 IYD) [68]. Bacteriophage \(\lambda\) cl protein (\(\lambda\)cI) plays a central role in the lytic to lysogenic growth switch and is able to both activate and repress transcription. For activation of transcription, \(\lambda\)cl binds just upstream of the \(-35\) element (class II transcription factor binding site) and interacts with \(\alpha\) domain 4 (\(\circ\)4).