Reconstructing prokaryotic transcriptional regulatory networks: lessons from actinobacteria

Abstract

Reconstruction of transcriptional regulatory networks of uncharacterized bacteria is a main challenge for the post-genomic era. Recent studies, including one in BMC Systems Biology, address this problem in the relatively underexplored actinobacteria clade, which includes major pathogenic and economically relevant taxa.

Figure 1

The transcription apparatus and transcription regulatory network of bacteria. (a) Schematic representation of the architecture of bacterial transcription machinery and operons and regulons. A regulon is the set of genes regulated by one transcription factor; an operon is a set of adjacent genes transcribed into one mRNA. (b) Architecture of transcription regulatory networks. The global structure (left) and three types of motifs found in transcription regulatory networks (right) are depicted as ordered graphs. Red dots indicate transcription factors; blue dots indicate targets. (c) The degree distribution of transcription factor-target interactions is approximated by a power-law equation [5]. The graph shows a power-law distribution; degree (d) is the number of regulatory connections between a transcription factor and target genes, while P(d) indicates the probability of transcription factors with a particular number of such connections. Pol, polymerase; TF, transcription factor; TFBS, transcription factor binding site.

Figure 2

Methods of network inference in uncharacterized prokaryotes. (a, b) Conventionally used methods for network reconstruction. (a) Orthology detection by comparison of transcription factor-target (TF-TG) links between species. Crosses indicate links known from the first species that are not found in the second species. (b) Position-specific weight matrices (PWMs) or hidden Markov models (HMMs) derived from binding site alignments (represented here by a grid) are used to predict target genes for conserved transcription factors. (c, d, e) The three recently published approaches to network reconstruction discussed here [7-9]. (c) The approach of Baumbach et al. [7]. (d) The approach of Balazsi et al. [8]. (e) The approach of Guo et al. [9]. Refer to the text for details of each of the studies (c-e) aimed at reconstructing actinobacterial transcription regulatory networks. Pol, polymerase; TFBS, transcription factor binding site.