Bacterial nucleoid organization is believed to have minimal influence on the global transcription program. Using an altered bacterial histone-like protein, HU␣, we show that reorganization of the nucleoid configuration can dynamically modulate the cellular transcription pattern. The mutant protein transformed the loosely packed nucleoid into a densely condensed structure. The nucleoid compaction, coupled with increased global DNA supercoiling, generated radical changes in the morphology, physiology, and metabolism of wild-type K-12 Escherichia coli. Many constitutive housekeeping genes involved in nutrient utilization were repressed, whereas many quiescent genes associated with virulence were activated in the mutant. We propose that, as in eukaryotes, the nucleoid architecture dictates the global transcription profile and, consequently, the behavior pattern in bacteria.bacterial HU ͉ nucleoid condensation ͉ virulence T he highly organized eukaryotic chromosome requires elaborate remodeling for coordination of transcription processes. The bacterial chromosome, however, constitutes a comparatively open and expanded structure, accessible throughout the cell cycle to DNA-binding proteins, polymerases, and ribosomes (1, 2). The apparent lack of a systemic hierarchy of nucleoid organization in bacteria was attributed to a low stability of histone-like protein-DNA complexes and the dynamic nature of the bacterial chromosome (3). In the absence of any perceptible higher-order chromosome organization imposing a general level of restriction on the accessibility of bacterial promoters, gene expression is believed to be regulated by operon-specific factors, adjacent DNA control elements and local DNA architecture; global nuclear organization is thought to contribute minimally to overall control of cellular processes involving DNA as substrate (4). Considering the exquisite precision with which bacteria can modulate their gene-expression profile to various environmental challenges, the ostensible lack of influence of chromosome organization over global gene regulation is surprising.Based on its small size, basic nature, cellular abundance, and sequence-independent DNA-binding capacity, the nucleoidassociated protein HU has long been characterized as the bacterial counterpart of eukaryotic histones (5). HU was initially attributed with the capability to form nucleosome-like structures in bacterial chromosomes (6), but subsequent studies have resulted in conflicting reports about the exact role of HU in chromosome compaction (7,8). In almost all bacteria except enterobacteriaciae, including Eschericiha coli, HU exists as an 18-kDa homodimer. In E. coli, HU is a heterodimer of two subunits, HU␣ and HU␤.Using a gain-of-function HU␣ mutant, we demonstrate that nucleoid structural reorganization in bacteria can directly induce a radical change in the gene-expression profile, resulting in dramatic changes in cellular morphology and physiology. Materials and MethodsBacterial Strains, Media, and Growth Conditions. Mutagenesis of HU␣ ...

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