Domian I J, Reisenauer A, Shapiro L
Department of Developmental Biology, Beckman Center, B300, Stanford University School of Medicine, Stanford, CA 94305-5329, USA.
Proc Natl Acad Sci U S A. 1999 Jun 8;96(12):6648-53. doi: 10.1073/pnas.96.12.6648.
The transcriptional regulator CtrA controls several key cell-cycle events in Caulobacter crescentus, including the initiation of DNA replication, DNA methylation, cell division, and flagellar biogenesis. CtrA is a member of the response regulator family of two component signal transduction systems. Caulobacter goes to great lengths to control the time and place of the activity of this critical regulatory factor during the cell cycle. These controls include temporally regulated transcription and phosphorylation and spatially restricted proteolysis. We report here that ctrA expression is under the control of two promoters: a promoter (P1) that is active only in the early predivisional cell and a stronger promoter (P2) that is active in the late predivisional cell. Both promoters exhibit CtrA-mediated feedback regulation: the early P1 promoter is negatively controlled by CtrA, and the late P2 promoter is under positive feedback control. The CtrA protein footprints conserved binding sites within the P1 and P2 promoters. We propose that the P1 promoter is activated after the initiation of DNA replication in the early predivisional cell. The ensuing accumulation of CtrA results in the activation of the P2 promoter and the repression of the P1 promoter late in the cell cycle. Thus, two transcriptional feedback loops coupled to cell cycle-regulated proteolysis and phosphorylation of the CtrA protein result in the pattern of CtrA activity required for the temporal and spatial control of multiple cell-cycle events.
转录调节因子CtrA控制新月柄杆菌中的几个关键细胞周期事件，包括DNA复制起始、DNA甲基化、细胞分裂和鞭毛生物合成。CtrA是双组分信号转导系统的应答调节因子家族成员。新月柄杆菌不遗余力地在细胞周期中控制这个关键调节因子活性的时间和位置。这些控制包括时间调控的转录和磷酸化以及空间受限的蛋白水解。我们在此报告，ctrA的表达受两个启动子的控制：一个启动子（P1）仅在分裂前早期细胞中活跃，另一个更强的启动子（P2）在分裂前晚期细胞中活跃。两个启动子均表现出CtrA介导的反馈调节：早期的P1启动子受CtrA负调控，晚期的P2启动子受正反馈调控。CtrA蛋白覆盖P1和P2启动子内的保守结合位点。我们提出，P1启动子在分裂前早期细胞中DNA复制起始后被激活。随后CtrA的积累导致P2启动子的激活以及细胞周期后期P1启动子的抑制。因此，两个转录反馈环与细胞周期调控的蛋白水解以及CtrA蛋白的磷酸化相结合，产生了对多个细胞周期事件进行时间和空间控制所需的CtrA活性模式。
