The CtrA response regulator mediates temporal control of gene expression during the Caulobacter cell cycle

In its role as a global response regulator, CtrA controls the transcription of a diverse group of genes at different times in the Caulobacter crescent us cell cycle. To understand the differential regulation of CtrA-controlled genes, we compared the expression of two of these genes, the fliQ flagella r gene and the ccrM DNA methyltransferase gene. Despite their similar promo ter architecture, these genes are transcribed at different times in the cel l cycle. PfliQ is activated earlier than PccrM. Phosphorylated CtrA (CtrA s imilar to P) bound to the CtrA recognition sequence in both promoters but h ad a 10 to 20-fold greater affinity for PfliQ. This difference in affinity correlates with temporal changes in the cellular levels of CtrA. Disrupting a unique inverted repeat element in PccrM significantly reduced promoter a ctivity but not the timing of transcription initiation, suggesting that the inverted repeat does not play a major role in the temporal control of ccrM expression. Our data indicate that differences in the affinity of CtrA sim ilar to P for PfliQ and PccrM regulate, in part, the temporal expression of these genes. However, the timing of fliQ transcription but not of ccrM tra nscription was altered in cells expressing a stable CtrA derivative, indica ting that changes in CtrA similar to P levels alone cannot govern the cell cycle transcription of these genes. We propose that changes in the cellular concentration of CtrA similar to P and its interaction with accessory prot eins influence the temporal expression of fliQ, ccrM and other key cell cyc le genes and ultimately the regulation of the cell cycle.