A computational study of bacterial gene regulation and adaptation ...

Intuitively negative supercoiling, by promoting DNA unwinding, should facilitate opencomplex formation and thus encourage transcription on a large scale. However, in contrast tothis expectation, a genome-scale survey of transcriptional response to inhibition of DNAgyrase (which creates negative supercoils) showed that just 8% of genes in E. coli, fromdiverse functional categories, are affected by this perturbation (Peter et al. 2004). A follow-upstudy expanded this list several fold, but still showed that genes can be both up- and downregulatedby the loss of negative supercoiling (Blot et al. 2006). It is thought that thisdeviation from expectation may be due to alterations in promoter topology; for example, thebipartite promoter elements may be aligned in a fashion that can be recognised by the RNAPholoenzyme only as a consequence of reduced negative supercoiling (Travers andMuskhelishvili 2005). It might also be due to altered binding of other transcriptionalregulators to the DNA. Further, at promoters which require negative supercoiling to allowopen-complex formation, supercoiling might induce gene expression noise leading todiversity in a cell population (Mitarai et al. 2008). In summary, supercoiling is a dynamic‘global second-messenger’ that controls gene expression (Peter et al. 2004).I.2.4. !-factorsThese are the most important trans components of the basal transcriptional machinery that isresponsible for transcription initiation. The !-factor recruits the RNAP holoenzyme to thepromoter and permits open complex formation. Genomic ChIP-chip analysis hassystematically confirmed earlier molecular studies showing that the !-factor is largelyreleased from the transcribing complex immediately after transcription initiation (Reppas etal. 2006); however, it is retained during elongation at selected promoters leading tospeculation on its role in controlling elongation at these genes (Kapanidis et al. 2005; Reppaset al. 2006).The most prominent !-factor in E. coli, responsible for initiation at many promoters, belongsto what is called the !70 family. In addition to this major !-factor, E. coli has six further !-factors, which bind to the RNAP under various conditions. However, as shown by a genomicstudy, there is substantial overlap between targets of different !-factors, raising questions onhow selectivity is achieved (Wade et al. 2006). One possibility is that alterations in the7