COMPARATIVE MECHANISMS FOR TRANSCRIPTION AND REGULATORY SIGNALS IN ARCHAEA AND BACTERIA

<p>A review and comparisosn of genetic regulatory mechanisms in archaea and bacteria.</p

Structural and functional map of a bacterial nucleoid

<p>Genome-wide mapping of transcription factor-DNA interactions in bacterial chromosomes in vivo has begun to reveal global zones occupied by these factors that serve two purposes: compacting the bacterial DNA and influencing global programs of gene transcription.</p

Effect of relative distance between TF and target genes on the degree of coexpression of the target genes.

<p>The coexpression behavior of genes that are coregulated by one TF is disentangled, depending on whether genes are equidistantly located (grey) or not equidistantly located (purple) relative to their common TF-coding gene. Y-axis displays the degree of coexpression (SCR), X-axis displays the maximum genomic distance between the coregulated genes.</p

The distance between coregulated genes negatively influences their coexpression degree.

<p>The plot shows the mean coexpression degree as a function of the maximum distance between two genes. The distance (x-axis) is measured by the number of kb (kilo base pairs, equal to 1000 base pairs) between the structural gene start positions of two genes. Coexpression degree (y-axis) is measured by the median SCR (a low median SCR implies high degree of coexpression) of genes with a distance lower or equal to the distance indicated on the x-axis. The effect of distance on coexpression is shown for all coregulated genes (dark-blue curve). Coexpression degree of coregulated genes can be compared to the negative control containing all genes not known to be coregulated (red curve). Note that breaks in the x-axis between distances <10 and <20 kb and between distances <100 and <500 correspond to scale differences. The numbers above each data point of the dark-blue curve represent the number of pairs of coregulated genes for which the median SCR was calculated.</p

Evolutionary conservation of distance between coregulated genes.

<p>The x-axis represents the pairwise genomic distance between coregulated genes in E. coli, measured in intervening genes. The y-axis represents the degree to which for coregulated genes in E. coli the genomic distance is evolutionarily conserved in other gamma-proteobacteria which is expressed as the fraction of orthologous gene pairs for which the distance is equal or smaller (y-axis) than the distance between the corresponding genes in E. coli (x-axis) over the total number of analyzed orthologous genes. Orthologous genes are pairs of genes in other species that are orthologous to a pair considered in E. coli, i.e. a pair of coregulated genes in E. coli is expected to have an orthologous counterpart in other gamma-proteobacterial species if both genes in the E. coli pair have an orthologous counterpart in the considered gamma-proteobacterial species. Results are shown for respectively pairs of genes that are highly coexpressed (SCR < 100) (black curve) versus pairs of genes that are not coexpressed (SCR > 1000) (blue curve).</p

The distance between coregulated genes has a larger influence on their coexpression degree if genes are less tightly coregulated.

<p>The coexpression behavior of coregulated genes was disentangled, depending on whether the regulatory programs displayed complete versus partial overlap (blue versus orange) and depending on the number of common TFs present in the overlapping part of their regulatory program (dotted line for 1 TF versus full line for >1 TF).</p

Internal-sensing machinery directs the activity of the regulatory network in Escherichia coli

<p>Individual cells need to discern and synchronize transcriptional responses according to variations in external and internal conditions. Metabolites and chemical compounds are sensed by transcription factors (TFs), which direct the corresponding specific transcriptional responses. We propose a classification of the currently known TFs of Escherichia coli based on whether they respond to metabolites incorporated from the exterior, to internally produced compounds, or to both. When analyzing the mutual interactions of TFs, the dominant role of internal signal sensing becomes apparent, greatly due to the role of global regulators of transcription. This work encompasses metabolite–TF interactions, bridging the gap between the metabolic and regulatory networks, thus advancing towards an integrated network model for the understanding of cellular behavior.</p

Frequency Matrices for the −10 and −35 Motifs of σ⁷⁰ Promoters in E. coli

<p>This matrix pair (Matrix_18_15_13_2_1.5) was selected for searching across bacterial genomes from a collection of optimized matrices defined for E. coli in [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0020185#pgen-0020185-b001" target="_blank">1</a>]. Note that in order to compare these matrices with the canonical patterns (TTGACA and TATAAT), the spacers of 13 bp to 19 bp between the two boxes correspond to the 15 bp to 21 bp reported in the literature, as the TGT triplet is considered as part of the −10 box. Before searching for promoter-like signals, these matrices were calibrated using the noncoding base composition of each target genome.</p

Internal Versus External Effector and Transcription Factor Gene Pairs Differ in Their Relative Chromosomal Position in Escherichia coli

<p>Here, we analyze the genome organization of the genetic components of these sensing systems, using the classification described earlier. We report the chromosomal proximity of transcription factors and their effector genes to sense periplasmic signals or transported metabolites (i.e. transcriptional sensing systems from the external class) in contrast to the components for sensing internally synthesized metabolites, which tend to be distant on the chromosome. We strengthen our finding that external sensing genetic machinery behaves like chromosomal modules of regulation to respond rapidly to variations in external conditions through co-expression of their genetic components, which is corroborated with microarray data for E. coli. Furthermore, we show several lines of evidence supporting the need for the coordinated activity of external sensing systems in contrast to that of internal sensing machinery, which can explain their close chromosomal organization. The observed functional correlation between the chromosomal organization and the genetic machinery for environmental sensing should contribute to our understanding of the logical functioning and evolution of the transcriptional regulatory networks in bacteria.</p

Schematic Representation of the Main Interactions of RNAP with Promoter DNA and Alignment of the σ⁷⁰ Motifs for Recognition and Binding of −10 (2.4 Region) and −35 Promoter Sequences (4.2 Region) for Representative Eubacteria

<p>Sequence alignments of several σ⁷⁰ factors from different bacteria reveal four conserved regions that can be further divided into subregions [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0020185#pgen-0020185-b039" target="_blank">39</a>]. Only regions 2 and 4 are well conserved in all members of the σ⁷⁰ family [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0020185#pgen-0020185-b040" target="_blank">40</a>–<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0020185#pgen-0020185-b043" target="_blank">43</a>] and include subregions involved in binding to the core RNAP complex, promoter melting, and recognition of the −10 and −35 promoter sequences (regions 2.4 and 4.2, respectively) [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0020185#pgen-0020185-b010" target="_blank">10</a>,<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0020185#pgen-0020185-b040" target="_blank">40</a>,<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0020185#pgen-0020185-b044" target="_blank">44</a>]. CLUSTALW was used to generate the alignment with default parameters (<a href="http://www.ebi.ac.uk/clustalw" target="_blank">http://www.ebi.ac.uk/clustalw</a>) [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0020185#pgen-0020185-b045" target="_blank">45</a>].</p