SlrA/SinR/SlrR inhibits motility gene expression upstream of a hypersensitive and hysteretic switch at the level of σ(D) in Bacillus subtilis.

<div class="line" id="line-15"> Exponentially growing <i> Bacillus subtilis </i> cultures are epigenetically differentiated into two subpopulations in which cells are either ON or OFF for &sigma;d&hyphen;dependent gene expression: a pattern suggestive of bistability. The gene encoding &sigma;D, <i> sigD </i> , is part of the 31&hyphen;gene <i> fla/che </i> operon where its location at the 3&prime; end, 25&emsp;kb away from the strong <i> Pfla/che </i> promoter, determines its expression level relative to a threshold. Here we show that addition of a single extra copy of the <i> slrA </i> gene in the chromosome inhibited &sigma;d&hyphen;dependent gene expression. SlrA together with SinR and SlrR reduced <i> sigD </i> transcript by potentiating a distance&hyphen;dependent decrease in <i> fla/che </i> operon transcript abundance that was not mediated by changes in expression from the <i> Pfla/che </i> promoter. Consistent with acting upstream of &sigma;D, SlrA/SinR/SlrR was bypassed by artificial ectopic expression of <i> sigD </i> and hysteretically maintained for 20 generations by engaging the <i> sigD </i> gene at the native locus. SlrA/SinR/SlrR was also bypassed by increasing <i> fla/che </i> transcription and resulted in a hypersensitive output in flagellin expression. Thus, flagellin gene expression demonstrated hypersensitivity and hysteresis and we conclude that &sigma;d&hyphen;dependent gene expression is bistable.</div>