Transcription factor family-based reconstruction of singleton regulons and study of the Crp/Fnr, ArsR, and GntR families in Desulfovibrionales genomes

Abstract

Accurate detection of transcriptional regulatory elements is essential for high-quality genome annotation, metabolic reconstruction, and modeling of regulatory networks. We developed a computational approach for reconstruction of regulons operated by transcription factors (TFs) from large protein families and applied this novel approach to three TF families in 10 Desulfovibrionales genomes. Phylogenetic analyses of 125 regulators from the ArsR, Crp/Fnr, and GntR families revealed that 65% of these regulators (termed reference TFs) are well conserved in Desulfovibrionales, while the remaining 35% of regulators (termed singleton TFs) are species specific and show a mosaic distribution. For regulon reconstruction in the group of singleton TFs, the standard orthology-based approach was inefficient, and thus, we developed a novel approach based on the simultaneous study of all homologous TFs from the same family in a group of genomes. As a result, we identified binding for 21 singleton TFs and for all reference TFs in all three analyzed families. Within each TF family we observed structural similarities between DNA-binding motifs of different reference and singleton TFs. The collection of reconstructed regulons is available at the RegPrecise database (http://regprecise.lbl.gov/RegPrecise/Desulfovibrionales.jsp).

Fig 1

Work flow for reconstruction of reference and singleton TF regulons within a single TF family.

Fig 2

Neighbor-joining tree of the Crp/Fnr-family TFs. The numbers represent bootstrap values obtained from 1,000 replicates. Orthologous groups of TFs are marked by colors. Groups of TFs that have common TF-binding motifs are marked by brackets.

Fig 3

Neighbor-joining tree of the ArsR-family TFs. The numbers represent bootstrap values obtained from 1,000 replicates. Orthologous groups of TFs are marked by colors. Groups of TFs that have common TF-binding motifs are marked by brackets.

Fig 4

Neighbor-joining tree of the GntR-family TFs. The numbers represent bootstrap values obtained from 1,000 replicates. Orthologous groups of TFs are marked by colors. Groups of TFs that have common TF-binding motifs are marked by brackets.