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

I.4. Transcriptional regulatory networks: structure and evolutionTranscription factors regulate the expression of only a specific set of genes because ofselectivity in the nature of DNA sequences they can recognise. Therefore, the associationbetween TFs and their target genes can be represented as networks where each edge isdirected from a TF to a target gene. Such data are available for nearly all TFs in the yeastSaccharomyces cerevisiae. These data, a majority of which comes from a single study, wereobtained using genome-wide ChIP-chip studies (Harbison et al. 2004). For E. coli, theRegulonDB database makes available all known transcriptional regulatory interactionsdescribed in the literature (Gama-Castro et al. 2008). The most recent release of this database(January 2009, version 6.3) contains 3,289 regulatory interactions between 166 TFs (notincluding !-factors) and 1,477 target genes. Recently, ChIP-chip studies have been performedon selected TFs in E. coli substantially adding to our current knowledge of regulatory targetsfor these TFs (Cho et al. 2008a; Cho et al. 2008b; Grainger et al. 2006; Grainger et al. 2005).But we still lack such information for a large proportion of TFs. The regulatory network inRegulonDB has been analysed as a whole and a number of biological insights have beenderived as a result. In this section, we review some of these, with emphasis on insights into(1) types of TFs, (2) modularity of network structure, (3) variation in network structure acrossdifferent functional target gene classes, (4) constraint imposed on genome organisation bytranscriptional regulation, (5) integration of signal sensing into the regulatory network and (6)evolution of regulatory interactions.I.4.1. Types of transcription factors:global and localIn the current release of RegulonDB, 10 TFs regulate two-thirds of all target genes in thedatabase. Previously, Martinez-Antonio and Collado-Vides performed a detailed study that setthe rules for defining global TFs (Martinez-Antonio and Collado-Vides 2003). These rules gobeyond the number of genes or operons regulated by a TF and include the following: (1)number of- and nature of co-regulating TFs, (2) ability to regulate genes which belong totarget-groups of different !-factors, (3) potential to respond to a wide range of environmentalconditions, and (4) capacity to target genes from a number of functional categories. In total,only seven TFs pass these criteria. These are the catabolite-responsive CRP, anaerobiosisregulators FNR and ArcA, the feast or famine LRP, and the histone-like FIS, IHF and H-NS.Of these, all except H-NS show an enrichment towards targeting genes from a single broad11