%AFitzgerald, Stephen%AKary, Stefani%AAlshabib, Ebtihal%AMacKenzie, Keith%AStoebel, Daniel M%AChao, Tzu-Chiao%ACameron, Andrew%Anull Ed.%BJournal Name: Nucleic Acids Research; Journal Volume: 48; Journal Issue: 18 %D2020%I %JJournal Name: Nucleic Acids Research; Journal Volume: 48; Journal Issue: 18 %K %MOSTI ID: 10273652 %PMedium: X %TRedefining the H-NS protein family: a diversity of specialized core and accessory forms exhibit hierarchical transcriptional network integration %XAbstract 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. %0Journal Article