Interactive regulation by the Bacillus subtilis global regulators CodY and ScoC

Abstract

SUMMARY CodY and ScoC are Bacillus subtilis transcriptional regulators that control the expression of dozens of genes and operons. Using scoC-lacZ fusions and DNA-binding experiments, we show here that scoC is directly repressed by CodY. This effect creates multiple forms of cascade regulation. For instance, expression of the dtpT gene, which is directly and negatively controlled by ScoC and encodes a putative oligopeptide permease, was activated indirectly by CodY due to CodY-mediated repression of scoC. The opp operon, which encodes an oligopeptide permease that is essential for sporulation and genetic competence development, proved to be a direct target of repression by both ScoC and CodY, but was not significantly affected in codY or scoC single mutants. The combined actions of CodY and ScoC maintain opp repression when either one of the regulators loses activity, but limit the level of repression to that provided by one of the regulators acting alone. Under conditions of nitrogen limitation, repression by ScoC of dtpT and opp was partly prevented by TnrA. Thus, the functioning of ScoC is determined by other transcription factors via modulation of its expression or DNA binding.

Interplay of CodY and ScoC in the Regulation of Major Extracellular Protease Genes of Bacillus subtilis

“…We concluded that both CodY and ScoC are strong repressors of the aprE gene and that each is sufficient for efficient repression in the absence of the other. Moreover, given that the difference in aprE expression between the codY ϩ scoC ϩ strain, BB3912, and the codY scoC double mutant strain, BB3910, was only 32-fold (Table 3), the effects of CodY and ScoC on aprE are not multiplicative, in accord with the previous observation that the two proteins do not act completely independently of each other due to scoC repression by CodY (41).…”

“…The procedures for gel shift and DNase I footprinting experiments were as described previously (41). Samples contained various amounts of proteins, a vast excess of unlabeled salmon sperm DNA, and Յ0.1 or 2 to 4 nM labeled DNA for gel shift or DNase I footprinting experiments, respectively.…”

“…As a result, the CodY-mediated regulation of some promoters, such as those of oppA and braB, which are under dual repression by CodY and ScoC, is not easily revealed by single mutations in codY or scoC (41,42).…”

“…A possible explanation is that CodY regulates the expression of a second regulator of the protease genes. In fact, both aprE and nprE are directly repressed by ScoC (12,16,18,23,37,38), a pleiotropic transcriptional regulator, which also controls expression of a minor extracellular protease (Epr), oligopeptide permeases, and other proteins (16,(39)(40)(41)(42).…”

CodY-Dependent Regulation of Sporulation in Clostridium difficile

“…ScoC directly downregulates opp, app, and sinIR expression (87,88), suggesting that ScoC may inhibit sporulation under high-nutrient conditions by repressing the expression of genes involved in early sporulation events. Further, CodY directly represses scoC transcription, and CodY and ScoC independently coregulate several loci, including opp (89,90). Altogether, these results imply that multiple regulators control B. subtilis sporulation through nutrient-dependent alteration of early sporulation gene expression.…”