The complex architecture of mycobacterial promoters

The genus Mycobacterium includes a variety of species with differing phenotypic properties, including growth rate, pathogenicity and environment- and host-specificity. Although many mycobacterial species have been extensively studied and their genomes sequenced, the reasons for phenotypic variation between closely related species remain unclear. Variation in gene expression may contribute to these characteristics and enable the bacteria to respond to changing environmental conditions. Gene expression is controlled primarily at the level of transcription, where the main element of regulation is the promoter. Transcriptional regulation and associated promoter sequences have been studied extensively in E. coli. This review describes the complex structure and characteristics of mycobacterial promoters, in comparison to the classical E. coli prokaryotic promoter structure. Some components of mycobacterial promoters are similar to those of E. coli. These include the predominant guanine residue at the transcriptional start point, conserved -10 hexamer, similar interhexameric distances, the use of ATG as a start codon, the guanine- and adenine-rich ribosome binding site and the presence of extended -10 (TGn) motifs in strong promoters. However, these components are much more variable in sequence in mycobacterial promoters and no conserved -35 hexamer sequence (clearly defined in E. coli) can be identified. This may be a result of the high G+C content of mycobacterial genomes, as well as the large number of sigma factors present in mycobacteria, which may recognise different promoter sequences. Mycobacteria possess a complex transcriptional regulatory network. Numerous regulatory motifs have been identified in mycobacterial promoters, predominantly in the interhexameric region. These are bound by specific transcriptional regulators in response to environmental changes. The combination of specific promoter sequences, transcriptional regulators and a variety of sigma factors enables rapid and specific responses to diverse conditions and different stages of infection. This review aims to provide an overview of the complex architecture of mycobacterial transcriptional regulation.