Genome-wide analysis of Fis binding in <i>Escherichia coli</i> indicates a causative role for A-/AT-tracts

<jats:p>We determined the genome-wide distribution of the nucleoid-associated protein Fis in <jats:italic>Escherichia coli</jats:italic> using chromatin immunoprecipitation coupled with high-resolution whole genome-tiling microarrays. We identified 894 Fis-associated regions across the <jats:italic>E. coli</jats:italic> genome. A significant number of these binding sites were found within open reading frames (33%) and between divergently transcribed transcripts (5%). Analysis indicates that A-tracts and AT-tracts are an important signal for preferred Fis-binding sites, and that A<jats:sub>6</jats:sub>-tracts in particular constitute a high-affinity signal that dictates Fis phasing in stretches of DNA containing multiple and variably spaced A-tracts and AT-tracts. Furthermore, we find evidence for an average of two Fis-binding regions per supercoiling domain in the chromosome of exponentially growing cells. Transcriptome analysis shows that ∼21% of genes are affected by the deletion of <jats:italic>fis</jats:italic>; however, the changes in magnitude are small. To address the differential Fis bindings under growth environment perturbation, ChIP-chip analysis was performed using cells grown under aerobic and anaerobic growth conditions. Interestingly, the Fis-binding regions are almost identical in aerobic and anaerobic growth conditions—indicating that the <jats:italic>E. coli</jats:italic> genome topology mediated by Fis is superficially identical in the two conditions. These novel results provide new insight into how Fis modulates DNA topology at a genome scale and thus advance our understanding of the architectural bases of the <jats:italic>E. coli</jats:italic> nucleoid.</jats:p>