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

Claudia L. Kleinman ^[1] ; Gabriela Sycz ^[2] ; Hernán R. Bonomi ^[2] ; Romina M. Rodríguez ^[2] ; Angeles Zorreguieta ^[2] ; Rodrigo Sieira ^[2]
1. [1] McGill University
  
  McGill University
  
  Canadá
2. [2] Fundación Instituto Leloir
  
  Fundación Instituto Leloir
  
  Argentina
Localización: Nucleic acids research, ISSN 0305-1048, Vol. 45, Nº. 10, 2017, págs. 5757-5769
Idioma: inglés
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Resumen
- 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.