Journal
NUCLEIC ACIDS RESEARCH
Volume 48, Issue 18, Pages 10184-10198Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkaa709
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Funding
- Natural Sciences and Engineering Research Council of Canada [RGPIN-435784-2013, RGPIN-2019-07135]
- Saskatchewan Health Research Foundation [2867]
- United States of AmericaNational Science Foundation [1716794]
- University of Regina
- Direct For Biological Sciences
- Div Of Molecular and Cellular Bioscience [1716794] Funding Source: National Science Foundation
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H-NS is a nucleoid structuring protein and global repressor of virulence and horizontally-acquired genes in bacteria. H-NS can interact with itself or with homologous proteins, but protein family diversity and regulatory network overlap remain poorly defined. Here, we present a comprehensive phylogenetic analysis that revealed deep-branching clades, dispelling the presumption that H-NS is the progenitor of varied molecular backups. Each clade is composed exclusively of either chromosome-encoded or plasmid-encoded proteins. On chromosomes, stpA and newly discovered hlpP are core genes in specific genera, whereas hfp and newly discovered hlpC are sporadically distributed. Six clades of H-NS plasmid proteins (Hpp) exhibit ancient and dedicated associations with plasmids, including three clades with fidelity for plasmid incompatibility groups H, F or X. A proliferation of H-NS homologs in Erwiniaceae includes the first observation of potentially co-dependent H-NS forms. Conversely, the observed diversification of oligomerization domains may facilitate stable co-existence of divergent homologs in a genome. Transcriptomic and proteomic analysis in Salmonella revealed regulatory crosstalk and hierarchical control of H-NS homologs. We also discovered that H-NS is both a repressor and activator of Salmonella Pathogenicity Island 1 gene expression, and both regulatory modes are restored by Sfh (HppH) in the absence of H-NS.
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