G-quadruplex motifs are functionally conserved in cis-regulatory regions of pathogenic bacteria: An in-silico evaluation

The role of G-quadruplexes in the cellular physiology of human pathogenesis is an intriguing area of research. Nonetheless, their functional roles and evolutionary conservation have not been compared comprehensively in pathogenic forms of various bacterial genera and species. In the current in silico study, we addressed the role of G-quadruplex-forming sequences (G4 motifs) in the context of cis regulation, expression variation, regulatory networks, gene orthology and ontology. Genome-wide screening across seven pathogenic genomes using the G4Hunter tool revealed the significant prevalence of G4 motifs in cis-regulatory regions compared to the intragenic regions. Significant conservation of G4 motifs was observed in the regulatory region of 300 orthologous genes. Further analysis of published ChIP-Seq data (Minch et al., 2015) of 91 DNA-binding proteins of the M. tuberculosis genome revealed significant links between G4 motifs and target sites of transcriptional regulators. Interestingly, the transcription factors entangled with virulence, in specific, CsoR, Rv0081, DevR/DosR, and TetR family are found to have G4 motifs in their target regulatory regions. Overall the current study applies positional-functional relationship computation to delve into the cis-regulation of G-quadruplex structures in the context of gene orthology in pathogenic bacteria. (c) 2021 Elsevier B.V. and Soci & eacute;t & eacute; Fran & ccedil;aise de Biochimie et Biologie Mol & eacute;culaire (SFBBM). All rights reserved.

Automated summary

The current in silico study revealed the significant prevalence and conservation of G-quadruplex-forming sequences (G4 motifs) in cis-regulatory regions of pathogenic genomes, as well as significant links between G4 motifs and target sites of transcriptional regulators in Mycobacterium tuberculosis. Transcription factors related to virulence were found to have G4 motifs in their target regulatory regions. Overall, the study applies positional-functional relationship computation to explore the cis-regulation of G-quadruplex structures in pathogenic bacteria.