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.
Highlights
Bacterial nucleoid remodeling dependent on conserved histone-like protein, HU is one of the determining factors in global gene regulation
We provide a holistic view of the molecular connections between HU–DNA interactions and the nucleoid architecture as it correlates to global regulation of bacterial gene expression during growth, stasis and under stress
3D genome organization is crucial for cellular behaviors and genetic transmission. 3D genome is highly dynamic[30,31] and its reconfiguration through an influence on gene expression is important, at least in some eukaryotes, for cellular differentiation during embryonic development[32]
Summary
Bacterial nucleoid remodeling dependent on conserved histone-like protein, HU is one of the determining factors in global gene regulation. Nucleoid remodeling during cell growth and environmental adaptation correlate with pH and ionic strength controlled molecular switch that regulated HUαα dependent intermolecular DNA bundling. Nucleoid remodeling facilitated by DNA organization activities of nucleoid-associated proteins (NAPs) is one of the determining factors of global gene regulation[1,2,3,4]. Using an X-ray based imaging technique called soft X-ray tomography (SXT)[16], we characterized the higher-order E. coli nucleoid organization in near-native state and revealed an effect of HU surface charges in its overall remodeling during cell growth and environmental adaptation. By means of next-generation RNA sequencing (RNA-Seq), we find a link between the nucleoid remodeling and changes in global transcription This integrative structural study explains how HU can regulate dynamic transformations during nucleoid remodeling as it correlates to global gene regulation
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