Research Description

We study mechanisms of transcription regulation by the histone-like nucleoid-structuring protein HNS in commensal and pathogenic Escherichia coli. Specifically, we focus on mechanisms of de-repression by the LysR-type and FixJ/NarL-type transcription regulators such as LeuO, BglJ-RcsB and others, and their role in regulatory networks controlling pathogenicity. In addition, we analyze the interdependence of repression by H-NS and the rate of transcription.

H-NS is an pleiotropic regulator and an architectural protein of the enterobacterial chromosome (the nucleoid), and it is important for silencing of loci acquired by horizontal gene transfer and for bacterial fitness. H-NS binds  to s AT-rich DNA and forms extended complexes by polymerization along the DNA ('stiffening') and by building DNA-HNS-DNA bridges ('bridging'). Formation of HNS-DNA complexes next to promoters represses transcription by occluding RNA polymerase or, as shown in some cases, by trapping RNA polymerase at the promoter.

Repression by HNS can be relieved locus-specifically by various mechanisms. Most commonly, binding of specific transcriptional regulators compete with H-NS or restructure the H-NS-nucleoprotein complex. Other mechanisms include locus specific changes of the DNA structure (bending), enhancement of the transcription rate, and possibly direct modulation of the H-NS activity by changes of the physiological conditions.

The LysR-type transcription factor LeuO and the heterodimer of the FixJ-type transcription factors BglJ-RcsB are known H-NS antagonists. These transcription factors are part of a regulatory network, related to control of bacterial virulence.