Nucleoid remodeling during environmental adaptation is regulated by HU-dependent DNA bundling

Abstract

Bacterial nucleoid remodeling dependent on conserved histone-like protein, HU is one of the determining factors in global gene regulation. By imaging of near-native, unlabeled E. coli cells by soft X-ray tomography, we show that HU remodels nucleoids by promoting the formation of a dense condensed core surrounded by less condensed isolated domains. Nucleoid remodeling during cell growth and environmental adaptation correlate with pH and ionic strength controlled molecular switch that regulated HUαα dependent intermolecular DNA bundling. Through crystallographic and solution-based studies we show that these effects mechanistically rely on HUαα promiscuity in forming multiple electrostatically driven multimerization interfaces. Changes in DNA bundling consequently affects gene expression globally, likely by constrained DNA supercoiling. Taken together our findings unveil a critical function of HU-DNA interaction in nucleoid remodeling that may serve as a general microbial mechanism for transcriptional regulation to synchronize genetic responses during the cell cycle and adapt to changing environments.

Self‐assembly of multi‐component mitochondrial nucleoids via phase separation

“…Mitochondria are originally derived from prokaryotes, and nucleoids are an evolutionarily ancient feature used to organize both prokaryotic and mitochondrial genomes (Dillon & Dorman, 2010). In support of a common organizational principle, bacterial genomes are packaged into nucleoid structures that have also been described to behave as fluids (Cunha, Woldringh et al, 2001), and some bacterial nucleoprotein complexes also undergo phase separation (Monterroso, Zorrilla et al, 2019;Remesh, Verma et al, 2020). Unlike TFAM, bacterial architectural nucleoid-associated proteins, including HU, histone-like nucleoid structuring protein (H-NS), factor for inversion stimulation (FIS), and the integration host factor (IHF), lack HMG domains as seen in TFAM, suggesting a multitude of molecular interactions can condense DNA (Kucej & Butow, 2007;Dillon & Dorman, 2010).…”

Defining composition and function of the rhizosphere microbiota of barley genotypes exposed to growth-limiting nitrogen supplies

“…Consequently, microbes capable of either degrading or metabolising these, host genotype-specific, compounds will have a competitive advantage in the barley rhizosphere. Conversely, the functional enrichment in the wild microbiota can be interpreted as an adaptive change in the transcriptional machinery required for microbial adaptation to limited nutrient availability, as observed in individual bacterial strains [48–50]. These data point at a resilient wild microbiota capable of “adjusting” to N starvation while the same condition triggers a stronger inter-organismal competition in the ‘Elite’ rhizosphere.…”

Separate physiological roles of specific and non-specific DNA binding of HU protein in Escherichia coli

“…The non-specific binding triggers multimerization of HUα 2 dimers, but not of HU dimers, resulting in three-dimensional intermolecular DNA bundling (Hammel et al, 2016). Controlled by ionic strength and pH, the intermolecular hydrogen bonds between residues E34K and K37 dictates the HUα 2 multimerization, potentially functioning as a molecular switch that regulates DNA bundling in an environment dependent manner (Hammel et al, 2016; Remesh et al, 2020).…”