RegulonDB version 7.0: transcriptional regulation of Escherichia coli K-12 integrated within genetic sensory response units (Gensor Units)

Abstract

RegulonDB (http://regulondb.ccg.unam.mx/) is the primary reference database of the best-known regulatory network of any free-living organism, that of Escherichia coli K-12. The major conceptual change since 3 years ago is an expanded biological context so that transcriptional regulation is now part of a unit that initiates with the signal and continues with the signal transduction to the core of regulation, modifying expression of the affected target genes responsible for the response. We call these genetic sensory response units, or Gensor Units. We have initiated their high-level curation, with graphic maps and superreactions with links to other databases. Additional connectivity uses expandable submaps. RegulonDB has summaries for every transcription factor (TF) and TF-binding sites with internal symmetry. Several DNA-binding motifs and their sizes have been redefined and relocated. In addition to data from the literature, we have incorporated our own information on transcription start sites (TSSs) and transcriptional units (TUs), obtained by using high-throughput whole-genome sequencing technologies. A new portable drawing tool for genomic features is also now available, as well as new ways to download the data, including web services, files for several relational database manager systems and text files including BioPAX format.

Figure 1.

GU map. The elementary GU includes the signal (i), the concatenated set of reactions (ii) that elicit a genetic switch (iii) to induce or repress the expression of genes involved in the response (iv). The target genes in this diagram code for gene products involved in the synthesis of the signal (from molecule X to the signal), the utilization (from the signal to molecule Y), and induction of the gene(s) involved in the transport of the external signal.

Figure 2.

AraC-arabinose GU. In the presence of l-arabinose, AraC activates transcription of genes that code for proteins necessary for utilization and transport of l-arabinose. In the absence of glucose CRP coregulates with AraC. The four GU elements are represented by different colors in the image: blue, the signal (i) and signal transduction (ii); yellow, genetic switch (iii); green, the response (iv).

Figure 3.

Signal transduction of the σ²⁴ (σ^E) GU. In the absence of stress, the sigma factor σ²⁴ is complexed with RssA and RssB in the inner membrane, but under envelope stress, misfolded proteins and lipoproteins appear in the periplasm. The lipoproteins release RssB from the complex RssB-rseA-σ²⁴, and then a proteolytic cascade starts when DegS, bound to unfolded proteins, partially degrades the RseA protein in the RseA-σ²⁴ complex, producing the RseA-1-108 polypeptide that is cleaved by RseP, and the complex is released from the inner membrane. In the cytoplasm, HslUV or Lon can degrade RseA, releasing σ²⁴, which can bind to core RNA polymerase to activate transcription of genes for maintaining cell envelope integrity. Another protease that also degrades RseA in the cytoplasm is ClpXP, but the protein SspB has to be bound to the RseA-1-108-RpoE complex. On the other hand, the rpoE gene, which forms part of the rpoE-rseAB operon, is induced by the TF CpxR, which is shown in the image as a submap in a gray box. The submap is expandable by clicking on it. Details of each reaction with supporting evidence and references are provided in the database.