Genes directly controlled by CtrA, a master regulator of the Caulobacter cell cycle

Abstract

Studies of the genetic network that controls the Caulobacter cell cycle have identified a response regulator, CtrA, that controls, directly or indirectly, one-quarter of the 553 cell cycle-regulated genes. We have performed in vivo genomic binding site analysis of the CtrA protein to identify which of these genes have regulatory regions bound directly by CtrA. By combining these data with previous global analysis of cell cycle transcription patterns and gene expression profiles of mutant ctrA strains, we have determined that CtrA directly regulates at least 95 genes. The total group of CtrA-regulated genes includes those involved in polar morphogenesis, DNA replication initiation, DNA methylation, cell division, and cell wall metabolism. Also among the genes in this notably large regulon are 14 that encode regulatory proteins, including 10 two-component signal transduction regulatory proteins. Identification of additional regulatory genes activated by CtrA will serve to directly connect new regulatory modules to the network controlling cell cycle progression.

The Caulobacter crescentus ctrA P1 promoter is essential for the coordination of cell cycle events that prevent the overinitiation of DNA replication

“…These transcription factors are themselves regulated at multiple levels to ensure that they perform critical functions only during the correct time of the cell cycle. In the cell cycle of the aquatic Gram-negative bacterium Caulobacter crescentus, three proteins (DnaA, GcrA and CtrA) control the expression of over 200 (Holtzendorff et al, 2004;Hottes et al, 2005;Laub et al, 2002) of Caulobacter's 553 cell cycle-regulated genes (Laub et al, 2000). The CcrM adenine DNA methyltranferase has been suggested as a fourth cell cycle master regulator for its effect on transcription via methylation of promoters, creating a complete core circuit (Collier et al, 2007).…”

A membrane metalloprotease participates in the sequential degradation of a Caulobacter polarity determinant

“…PodJ has been shown to be a localization factor involved in polar morphogenesis (Viollier et al ., 2002a;Hinz et al ., 2003) whose expression is regulated by the cyclic variation in CtrA and GcrA levels (Crymes et al ., 1999;Laub et al ., 2002;Holtzendorff et al ., 2004). PodJ undergoes defined proteolytic processing (Viollier et al ., 2002a;Hinz et al ., 2003), with both the long form, PodJ L , and the short form, PodJ S , controlling different aspects of polar organelle development (Viollier et al ., 2002a).…”

A phospho-signaling pathway controls the localization and activity of a protease complex critical for bacterial cell cycle progression

“…1B). In its role as a DNA-binding regulatory protein, the active phosphorylated form of CtrA, CtrAϳP, directly controls the transcription of at least 95 cell cycle-regulated genes (5,6). In swarmer cells, CtrAϳP also represses initiation of chromosome replication by binding to five sites in the origin of replication (7).…”