RegPrecise 3.0 – A resource for genome-scale exploration of transcriptional regulation in bacteria

Abstract

BackgroundGenome-scale prediction of gene regulation and reconstruction of transcriptional regulatory networks in prokaryotes is one of the critical tasks of modern genomics. Bacteria from different taxonomic groups, whose lifestyles and natural environments are substantially different, possess highly diverged transcriptional regulatory networks. The comparative genomics approaches are useful for in silico reconstruction of bacterial regulons and networks operated by both transcription factors (TFs) and RNA regulatory elements (riboswitches).DescriptionRegPrecise (http://regprecise.lbl.gov) is a web resource for collection, visualization and analysis of transcriptional regulons reconstructed by comparative genomics. We significantly expanded a reference collection of manually curated regulons we introduced earlier. RegPrecise 3.0 provides access to inferred regulatory interactions organized by phylogenetic, structural and functional properties. Taxonomy-specific collections include 781 TF regulogs inferred in more than 160 genomes representing 14 taxonomic groups of Bacteria. TF-specific collections include regulogs for a selected subset of 40 TFs reconstructed across more than 30 taxonomic lineages. Novel collections of regulons operated by RNA regulatory elements (riboswitches) include near 400 regulogs inferred in 24 bacterial lineages. RegPrecise 3.0 provides four classifications of the reference regulons implemented as controlled vocabularies: 55 TF protein families; 43 RNA motif families; ~150 biological processes or metabolic pathways; and ~200 effectors or environmental signals. Genome-wide visualization of regulatory networks and metabolic pathways covered by the reference regulons are available for all studied genomes. A separate section of RegPrecise 3.0 contains draft regulatory networks in 640 genomes obtained by an conservative propagation of the reference regulons to closely related genomes.ConclusionsRegPrecise 3.0 gives access to the transcriptional regulons reconstructed in bacterial genomes. Analytical capabilities include exploration of: regulon content, structure and function; TF binding site motifs; conservation and variations in genome-wide regulatory networks across all taxonomic groups of Bacteria. RegPrecise 3.0 was selected as a core resource on transcriptional regulation of the Department of Energy Systems Biology Knowledgebase, an emerging software and data environment designed to enable researchers to collaboratively generate, test and share new hypotheses about gene and protein functions, perform large-scale analyses, and model interactions in microbes, plants, and their communities.

High-Resolution Specificity from DNA Sequencing Highlights Alternative Modes of Lac Repressor Binding

“…Although an alternative operator with a 2-bp spacer has a somewhat higher affinity, all of the known lac operators from many different species maintain the same asymmetric site (Novichkov et al 2013). No other members of the LacI/GalR family are known to bind asymmetric motifs, and even most variants of the lac repressor that bind with high affinity to the L2L9 site do not bind with high affinity to O1 (Daber and Lewis 2009).…”

“…The LacI/GalR family of transcription factors has many known and predicted binding site motifs (Novichkov et al 2013), nearly all of them symmetric with a CG central pair. However, since many of those motifs are predicted based on comparative analyses that often assume symmetry, it is plausible that more members of the LacI/GalR family might also have flexible binding specificities that allow for variable length spacers and asymmetric binding sites.…”

Comparative Genomics of DtxR Family Regulons for Metal Homeostasis in Archaea

“…Conservation of the DtxR-TF motifs across large phylogenetic distances allowed us to suggest that DtxR is an ancient family of TFs common to Bacteria and Archaea. A large-scale phylogenetic analysis of the previously studied DtxR family proteins from Bacteria (as captured in the RegPrecise database of transcriptional regulons [65]) and the archaeal DtxR-TFs (data not shown) identifies multiple branches of bacterial regulators that mixed with numerous groups of archaeal regulators, suggesting that the DtxR family was a frequent subject of various evolutionary processes, including divergent evolution (diversification of DNA motifs and effector specificities after duplication) and convergent evolution (appearance of a similar DNA motif in distantly related branches).…”

A glyS T-box riboswitch with species-specific structural features responding to both proteinogenic and nonproteinogenic tRNAGly isoacceptors

“…1). Analysis using the RegPrecise 3.0 database indicated that the S. aureus glyS T-box exhibited a very low score of conservation (12.9) compared with the other T-boxes which exhibit significantly higher scores (above 60) (Novichkov et al 2013). To clarify whether the ∼340-nt upstream of the glyS start codon region was part of its 5 ′ UTR, we tested its expression under minimal growth conditions (M9 mineral salt medium supplemented with amino acids, see Materials and Methods).…”

“…The region containing the T-box sequence [Score:12.9%, Position: −162] upstream of the S. aureus glyS coding region was identified using RegPrecise database prediction (Novichkov et al 2013). The broader full-length region upstream of the S. aureus glyS gene (SA1394), which includes the T-box sequence, was further verified using the KEGG database tool (Tanabe and Kanehisa 2012) and "The T-box search pattern" (Vitreschak et al 2008).…”