The quorum-sensing regulator ComA from Bacillus subtilis activates transcription using topologically distinct DNA motifs

Nucleic Acids Res. 2016 Mar 18;44(5):2160-72. doi: 10.1093/nar/gkv1242. Epub 2015 Nov 17.


ComA-like transcription factors regulate the quorum response in numerous Gram-positive bacteria. ComA proteins belong to the tetrahelical helix-turn-helix superfamily of transcriptional activators, which bind as homodimers to inverted sequence repeats in the DNA. Here, we report that ComA from Bacillus subtilis recognizes a topologically distinct motif, in which the binding elements form a direct repeat. We provide in vitro and in vivo evidence that the canonical and non-canonical site play an important role in facilitating type I and type II promoter activation, respectively, by interacting with different subunits of RNA polymerase. We furthermore show that there is a variety of contexts in which the non-canonical site can occur and identify new direct target genes that are located within the integrative and conjugative element ICEBs1. We therefore suggest that ComA acts as a multifunctional transcriptional activator and provides a striking example for complexity in protein-DNA interactions that evolved in the context of quorum sensing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacillus subtilis / genetics
  • Bacillus subtilis / metabolism
  • Bacterial Proteins / genetics*
  • Bacterial Proteins / metabolism
  • Base Sequence
  • Binding Sites
  • Cloning, Molecular
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • DNA-Directed RNA Polymerases / genetics*
  • DNA-Directed RNA Polymerases / metabolism
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Gene Expression Regulation, Bacterial*
  • Inverted Repeat Sequences
  • Molecular Sequence Data
  • Nucleotide Motifs
  • Promoter Regions, Genetic
  • Protein Binding
  • Protein Multimerization
  • Protein Subunits / genetics*
  • Protein Subunits / metabolism
  • Quorum Sensing / genetics*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Transcriptional Activation*


  • Bacterial Proteins
  • ComA protein, Bacteria
  • DNA-Binding Proteins
  • Protein Subunits
  • Recombinant Proteins
  • DNA-Directed RNA Polymerases