ChIP-seq analysis of the LuxR-type regulator VjbR reveals novel insights into the Brucella virulence gene expression network

Nucleic Acids Res. 2017 Jun 2;45(10):5757-5769. doi: 10.1093/nar/gkx165.

Abstract

LuxR-type transcription factors control diverse physiological functions necessary for bacterial adaptation to environmental changes. In the intracellular pathogen Brucella, the LuxR homolog VjbR has been shown to regulate the expression of virulence factors acting at early stages of the intracellular infection and, directly or indirectly, hundreds of additional genes. However, the precise determination of VjbR direct targets has so far proved elusive. Here, we performed chromatin immunoprecipitation of VjbR followed by next-generation sequencing (ChIP-seq). We detected a large amount of VjbR-binding sites distributed across the Brucella genome and determined a markedly asymmetric binding consensus motif, an unusual feature among LuxR-type regulators. RNA-seq analysis performed under conditions mimicking the eukaryotic intracellular environment revealed that, among all loci associated to VjbR-binding, this regulator directly modulated the expression of only a subset of genes encoding functions consistent with an intracellular adaptation strategy for survival during the initial stages of the host cell infection. Other VjbR-binding events, however, showed to be dissociated from transcription and may require different environmental signals to produce a transcriptional output. Taken together, our results bring new insights into the extent and functionality of LuxR-type-related transcriptional networks.

MeSH terms

  • Bacterial Proteins / genetics*
  • Bacterial Proteins / metabolism
  • Binding Sites
  • Brucella abortus / genetics*
  • Brucella abortus / metabolism
  • Brucella abortus / pathogenicity*
  • Chromatin Immunoprecipitation
  • Gene Expression Regulation, Bacterial*
  • Gene Regulatory Networks*
  • High-Throughput Nucleotide Sequencing
  • Nucleotide Motifs
  • Protein Binding
  • Quorum Sensing / genetics
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism
  • Trans-Activators / genetics*
  • Trans-Activators / metabolism
  • Transcription, Genetic
  • Virulence

Substances

  • Bacterial Proteins
  • Repressor Proteins
  • Trans-Activators
  • LuxR autoinducer binding proteins