title: Cell cycle progression in Caulobacter requires a nucleoid-associated protein with high AT sequence recognition.
abstract: Faithful cell cycle progression in the dimorphic bacterium Caulobacter crescentus requires spatiotemporal regulation of gene expression and cell pole differentiation. We discovered an essential DNA-associated protein, GapR, that is required for Caulobacter growth and asymmetric division. GapR interacts with adenine and thymine (AT)-rich chromosomal loci, associates with the promoter regions of cell cycle-regulated genes, and shares hundreds of recognition sites in common with known master regulators of cell cycle-dependent gene expression. GapR target loci are especially enriched in binding sites for the transcription factors GcrA and CtrA and overlap with nearly all of the binding sites for MucR1, a regulator that controls the establishment of swarmer cell fate. Despite constitutive synthesis, GapR accumulates preferentially in the swarmer compartment of the predivisional cell. Homologs of GapR, which are ubiquitous among the α-proteobacteria and are encoded on multiple bacteriophage genomes, also accumulate in the predivisional cell swarmer compartment when expressed in Caulobacter The Escherichia coli nucleoid-associated protein H-NS, like GapR, selectively associates with AT-rich DNA, yet it does not localize preferentially to the swarmer compartment when expressed exogenously in Caulobacter, suggesting that recognition of AT-rich DNA is not sufficient for the asymmetric accumulation of GapR. Further, GapR does not silence the expression of H-NS target genes when expressed in E. coli, suggesting that GapR and H-NS have distinct functions. We propose that Caulobacter has co-opted a nucleoid-associated protein with high AT recognition to serve as a mediator of cell cycle progression.
authors.affiliation: Department of Developmental Biology, Stanford University, Stanford, CA 94305.
authors.forename: Dante P
authors.initials: DP
authors.lastname: Ricci
authors.affiliation: Department of Developmental Biology, Stanford University, Stanford, CA 94305; Department of Chemistry, Stanford University, Stanford, CA 94305.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Melfi
authors.affiliation: Department of Developmental Biology, Stanford University, Stanford, CA 94305.
authors.forename: Keren
authors.initials: K
authors.lastname: Lasker
authors.affiliation: Department of Computer Science, Stanford University, Stanford, CA 94305.
authors.forename: David L
authors.initials: DL
authors.lastname: Dill
authors.affiliation: Department of Developmental Biology, Stanford University, Stanford, CA 94305.
authors.forename: Harley H
authors.initials: HH
authors.lastname: McAdams
authors.affiliation: Department of Developmental Biology, Stanford University, Stanford, CA 94305; shapiro@stanford.edu.
authors.forename: Lucy
authors.initials: L
authors.lastname: Shapiro
mesh_terms: D020856:AT Rich Sequence / Q000235:genetics*; D020561:Alphaproteobacteria / Q000378:metabolism; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D001483:Base Sequence; D016935:Caulobacter crescentus / Q000166:cytology* / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D002876:Chromosomes, Bacterial / Q000378:metabolism; D004269:DNA, Bacterial / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D004926:Escherichia coli / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D056426:Genetic Loci; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D000072417:Protein Domains; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D013347:Subcellular Fractions / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; D012333:RNA, Messenger
keywords: AT-rich; Caulobacter; asymmetry; cell cycle; nucleoid-associated protein