Interplay between three global regulatory proteins mediates oxygen regulation of the Escherichia coli cytochrome d oxidase (cydAB) operon

The Escherichia coli cydAB operon, encoding the subunits of the high-affini ty cytochrome d oxidase, is maximally transcribed in microaerobiosis as a r esult of the combined action of the oxygen-responsive regulators Fnr and Ar cA. Here, we report that the histone-like protein H-NS is an aerobic repres sor of cydAB expression. ArcA is shown to antagonize H-NS action to render cydAB expression insensitive to H-NS repression in anaerobiosis. The target s for H-NS-mediated aerobic repression are the four oxygen-regulated promot ers, designated P1, P2, P3 and P4. H-NS control is the result of H-NS bindi ng to an extended region within the cydAB promoter element, including seque nces upstream from and overlapping the four regulated promoters. We propose a regulatory model in which oxygen control of cydAB transcription is media ted by three alternative protein-DNA complexes that are assembled sequentia lly on the promoter region as the cells are shifted from aerobic to microae robic and to anaerobic conditions. According to this model, ArcA-P plays a central role in cydAB regulation by antagonizing H-NS repression of cydAB t ranscription when oxygen becomes limiting. This allows peak gene expression and subsequent repression by Fnr under fully anaerobic conditions.