## 2 Transcriptional Regulation in Integrons
### Regulation of Integrase Transcription in MI and CI by Stress Response Mechanisms
#### 2.5.4 The Role of Other Stress Response Regulators  
Bacteria frequently face environmental changes to which they reshape by using alternative \(\sigma\) factors, such as RpoS, to differentially express their genes. RpoS is a central regulator of the general stress response, and one of the major transcriptional regulators of the genes required for bacterial adaptation. Transcription of _rpoS_ in _Pseudomonas_ spp. is regulated by PsrA, and a recent study demonstrated that RpoS and PsrA were involved with the upregulation of integrase transcription in this genus. Since the _intII_ gene lacks PsrA and RpoS binding motifs [112], it has been proposed that RpoS and PsrA regulators indirectly regulated _intII_ transcription. In fact, [PERSON] et al. [113] verified that in conditions of stress response during the stationary phase, PsrA and RpoS indirectly stimulated _intII_ transcription through regulation of _lexA_ expression in association with additional regulators. It has been demonstrated that _psrA_ and _lexA_ genes share the same intergenic region that is targeted by PsrA. In this way, PsrA blocks its own promoter by preventing the binding of the RNA polymerase. However, at the same time, the binding of PsrA leads to a conformational structure modification that facilitates the RNA polymerase binding to the  
Figure 10: Sequence and organization of the P\({}_{\text{intIA}}\) promoter and the LexA and cAMP-CRP binding sites in the _attIA_ of the _V. cholerae_ chromosomal integrin. The CRP and the LexA binding sites are boxed and shaded in grey, respectively. The _intIA_ transcriptional start site (TSS) is featured in bold and a broken arrow. The P\({}_{\text{intIA}}\) –10 and –35 hexamers are highlighted.  
opposite chain, inducing _lexA_ transcription. In this way, PsrA upregulates the transcription of the _lexA_ gene while simultaneously repressing its own expression, ultimately leading to integrase transcription [113]. Additionally, [PERSON] et al. [20] identified binding sites for the nucleoid proteins H-NS, IHF, and FIS in and near the integrase (P\({}_{\text{intII}}\)) and cassette promoters (Pc/Pc + P2), which differentially regulated _intII_ expression in class 1 integrins. This regulatory mechanism will be discussed in more detail below since it involves the simultaneous regulation of P\({}_{\text{intII}}\) and Pc promoters.  
Finally, here, we compiled overall information from previous studies concerning the complex regulatory network of integrins. It was demonstrated that integrase genes are multiply regulated by different environmental conditions (temperature, salinity, growth phase), by mechanisms of the stress response (SOS system, cAMP-CRP regulon, stringent response, and RpoS), and by global regulators involved with several physiologic and metabolic pathways (FIS, H-NS, and IHF) [17; 18; 19; 20; 21; 22; 23; 24; 25; 26; 27; 28; 29; 107; 113]. Therefore, these findings altogether clearly demonstrated the elegant and intimate interplay of the external environment and host cell physiology with genetic adaptability and integron dynamics.