GntR Family of Bacterial Transcription Factors and Their DNA Binding Motifs: Structure, Positioning and Co-Evolution.

The GNTR family of transcription factors (TFs) is a large group of proteins present in diverse bacteria and regulating various biological processes. Here we use the comparative genomics approach to reconstruct regulons and identify binding motifs of regulators from three subfamilies of the GNTR family, FADR, HUTC, and YTRA. Using these data, we attempt to predict DNA-protein contacts by analyzing correlations between binding motifs in DNA and amino acid sequences of TFs. We identify pairs of positions with high correlation between amino acids and nucleotides for FADR, HUTC, and YTRA subfamilies and show that the most predicted DNA-protein interactions are quite similar in all subfamilies and conform well to the experimentally identified contacts formed by FadR from E. coli and AraR from B. subtilis. The most frequent predicted contacts in the analyzed subfamilies are Arg-G, Asn-A, Asp-C. We also analyze the divergon structure and preferred site positions relative to regulated genes in the FADR and HUTC subfamilies. A single site in a divergon usually regulates both operons and is approximately in the middle of the intergenic area. Double sites are either involved in the co-operative regulation of both operons and then are in the center of the intergenic area, or each site in the pair independently regulates its own operon and tends to be near it. We also identify additional candidate TF-binding boxes near palindromic binding sites of TFs from the FADR, HUTC, and YTRA subfamilies, which may play role in the binding of additional TF-subunits.