Molecular basis for the adaptive evolution of environment-sensing by H-NS proteins

Abstract

The DNA-binding protein H-NS is a pleiotropic gene regulator in gram-negative bacteria. Through its capacity to sense temperature and other environmental factors, H-NS allows pathogens like Salmonella to adapt their gene expression to their presence inside or outside warm-blooded hosts. To investigate how this sensing mechanism may have evolved to fit different bacterial lifestyles, we compared H-NS orthologs from bacteria that infect humans, plants, and insects, and from bacteria that live on a deep-sea hypothermal vent. The combination of biophysical characterization, high-resolution proton-less nuclear magnetic resonance spectroscopy, and molecular simulations revealed, at an atomistic level, how the same general mechanism was adapted to specific habitats and lifestyles. In particular, we demonstrate how environment-sensing characteristics arise from specifically positioned intra- or intermolecular electrostatic interactions. Our integrative approach clarified the exact modus operandi for H-NS-mediated environmental sensing and suggested that this sensing mechanism resulted from the exaptation of an ancestral protein feature.

Relationship between the Chromosome Structural Dynamics and Gene Expression—A Chicken and Egg Dilemma?

“…H-NS (h istone-like n ucleoid- s tructuring protein) is considered a global modulator of genes involved in adaptive processes related to changes in environmental conditions. DNA binding by H-NS is sensitive to environmental factors and DNA supercoiling states [ 1 , 15 , 30 , 35 ]. It binds cooperatively to AT-rich sequences to silence transcription [ 36 , 37 ].…”

“…It remains unclear whether H-NS primarily bridges or extends the DNA in vivo or whether these binding modes are mutually exclusive [ 43 ]. A more recent study revealed that H-NS-mediated environmental sensing operates mainly through its dimerization site2 located, as well as the dimerization site1, in the N-terminal domain of the protein [ 35 , 44 ]. The combination of site1 and site2 allows H-NS to multimerize and stably coat DNA with resultant gene silencing, whereas the unfolding of site2 at elevated temperature, high salinity or acidic pH results in an autoinhibited conformation incapable of stably interacting with DNA [ 35 , 45 ].…”

Bacterial H-NS contacts DNA at the same irregularly spaced sites in both bridged and hemi-sequestered linear filaments

“…DBDs alternating in orientation, or on and off DNA, could explain why some DBD–DRE contacts appear weak or as “shadow” contacts offset by ~5 bp (Figures 6 and S12). This fluid and irregular character of DBD contacts may help H-NS vary the extent of gene silencing as a function of cellular composition, temperature, and H-NS modulators like Hha (Boudreau et al, 2018; Kotlajich et al, 2015; Qin et al, 2020; van der Valk et al, 2017; Zhao et al, 2021a; Zhao et al, 2021b).…”

“…However, only bridged but not linear filaments inhibit transcript elongation by RNAP, which is proposed to occur via a topological trapping mechanism (Figures 1A and S1) (Boudreau et al, 2018; Kotlajich et al, 2015). Switching between linear and bridged states, DNA avidity, and thus H-NS effects on gene expression may be modulated in vivo by changes in H-NS levels, H-NS filament modifiers like Hha, cellular solutes and thus environmental conditions, and temperature (Boudreau et al, 2018; Kotlajich et al, 2015; Qin et al, 2020; van der Valk et al, 2017; Zhao et al, 2021a; Zhao et al, 2021b).…”

Special Issue: Role of Bacterial Chromatin in Environmental Sensing, Adaptation and Evolution

“…Due to interplay between genome organization and DNA transactions, these factors play specific and generic roles in processes such as transcription, replication, repair and chromosome segregation [4][5][6]. Environmental signals altering genome organization thus drive adaptive responses to changes in environment [7][8][9][10]. Additionally, it has become clear that genomic incorporation and maintenance of foreign DNA is facilitated by factors involved in silencing expression of foreign DNA (xenogeneic silencing) until relieved by specific signals [11].…”