Research Scientific Center for Bioinformatics, A.A. Kharkevich Institute for Information Transmission Problems, Russian Academy of Sciences Moscow, Russia.
Research Scientific Center for Bioinformatics, A.A. Kharkevich Institute for Information Transmission Problems, Russian Academy of Sciences Moscow, Russia ; Faculty of Bioengineering and Bioinformatics, Moscow State University Moscow, Russia.
Front Microbiol. 2014 Jun 11;5:294. doi: 10.3389/fmicb.2014.00294. eCollection 2014.
DNA-binding transcription factors (TFs) are essential components of transcriptional regulatory networks in bacteria. LacI-family TFs (LacI-TFs) are broadly distributed among certain lineages of bacteria. The majority of characterized LacI-TFs sense sugar effectors and regulate carbohydrate utilization genes. The comparative genomics approaches enable in silico identification of TF-binding sites and regulon reconstruction. To study the function and evolution of LacI-TFs, we performed genomics-based reconstruction and comparative analysis of their regulons. For over 1300 LacI-TFs from over 270 bacterial genomes, we predicted their cognate DNA-binding motifs and identified target genes. Using the genome context and metabolic subsystem analyses of reconstructed regulons, we tentatively assigned functional roles and predicted candidate effectors for 78 and 67% of the analyzed LacI-TFs, respectively. Nearly 90% of the studied LacI-TFs are local regulators of sugar utilization pathways, whereas the remaining 125 global regulators control large and diverse sets of metabolic genes. The global LacI-TFs include the previously known regulators CcpA in Firmicutes, FruR in Enterobacteria, and PurR in Gammaproteobacteria, as well as the three novel regulators-GluR, GapR, and PckR-that are predicted to control the central carbohydrate metabolism in three lineages of Alphaproteobacteria. Phylogenetic analysis of regulators combined with the reconstructed regulons provides a model of evolutionary diversification of the LacI protein family. The obtained genomic collection of in silico reconstructed LacI-TF regulons in bacteria is available in the RegPrecise database (http://regprecise.lbl.gov). It provides a framework for future structural and functional classification of the LacI protein family and identification of molecular determinants of the DNA and ligand specificity. The inferred regulons can be also used for functional gene annotation and reconstruction of sugar catabolic networks in diverse bacterial lineages.
DNA 结合转录因子（TFs）是细菌转录调控网络的重要组成部分。LacI 家族 TFs（LacI-TFs）广泛分布于某些细菌谱系中。大多数已鉴定的 LacI-TFs 感应糖效应物并调节碳水化合物利用基因。比较基因组学方法可实现 TF 结合位点的计算机识别和调控子的重建。为了研究 LacI-TFs 的功能和进化，我们进行了基于基因组学的调控子重建和比较分析。在来自 270 多个细菌基因组的超过 1300 个 LacI-TFs 中，我们预测了它们的同源 DNA 结合基序并鉴定了靶基因。通过重建调控子的基因组上下文和代谢子系统分析，我们分别对 78%和 67%的分析 LacI-TFs 临时分配了功能角色并预测了候选效应物。研究的 LacI-TFs 中近 90%是糖利用途径的局部调控因子，而其余 125 个全局调控因子控制着大量不同的代谢基因。全局 LacI-TFs 包括厚壁菌门中的 CcpA、肠杆菌科中的 FruR 和 Gamma 变形菌门中的 PurR，以及三个新预测的调控因子-GluR、GapR 和 PckR-它们被预测控制 Alpha 变形菌三个谱系的中心碳水化合物代谢。结合重建调控子的调控因子系统发育分析提供了 LacI 蛋白家族进化多样化的模型。在细菌中通过计算机重建的 LacI-TF 调控子的获得的基因组集合可在 RegPrecise 数据库（http://regprecise.lbl.gov）中获得。它为未来 LacI 蛋白家族的结构和功能分类以及 DNA 和配体特异性的分子决定因素的鉴定提供了框架。推断的调控子也可用于不同细菌谱系中功能基因注释和糖分解代谢网络的重建。
