Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Suvorova IA

PROVIDER: S-EPMC4494728 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Publications

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

Suvorova Inna A IA Korostelev Yuri D YD Gelfand Mikhail S MS

PloS one 20150707 7

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 pos ...[more]

PMID: 26151451

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Project description:BackgroundThe use of global gene expression profiling is a well established approach to understand biological processes. One of the major goals of these investigations is to identify sets of genes with similar expression patterns. Such gene signatures may be very informative and reveal new aspects of particular biological processes. A logical and systematic next step is to reduce the identified gene signatures to the regulatory components that induce the relevant gene expression changes. A central issue in this context is to identify transcription factors, or transcription factor binding sites (TFBS), likely to be of importance for the expression of the gene signatures.ResultsWe develop a strategy that efficiently produces TFBS/promoter databases based on user-defined criteria. The resulting databases constitute all genes in the Santa Cruz database and the positions for all TFBS provided by the user as position weight matrices. These databases are then used for two purposes, to identify significant TFBS in the promoters in sets of genes and to identify clusters of co-occurring TFBS. We use two criteria for significance, significantly enriched TFBS in terms of total number of binding sites for the promoters, and significantly present TFBS in terms of the fraction of promoters with binding sites. Significant TFBS are identified by a re-sampling procedure in which the query gene set is compared with typically 10(5) gene lists of similar size randomly drawn from the TFBS/promoter database. We apply this strategy to a large number of published ChIP-Chip data sets and show that the proposed approach faithfully reproduces ChIP-Chip results. The strategy also identifies relevant TFBS when analyzing gene signatures obtained from the MSigDB database. In addition, we show that several TFBS are highly correlated and that co-occurring TFBS define functionally related sets of genes.ConclusionsThe presented approach of promoter analysis faithfully reproduces the results from several ChIP-Chip and MigDB derived gene sets and hence may prove to be an important method in the analysis of gene signatures obtained through ChIP-Chip or global gene expression experiments. We show that TFBS are organized in clusters of co-occurring TFBS that together define highly coherent sets of genes.

Dataset Information

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

Publications

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

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