title: Regulation of the pap epigenetic switch by CpxAR: phosphorylated CpxR inhibits transition to the phase ON state by competition with Lrp.
abstract: Pap pili gene expression is controlled by a reversible OFF/ON phase switch that is orchestrated by binding of Lrp to pap pilin promoter proximal sites 1, 2, and 3 (OFF) or pap promoter distal sites 4, 5, and 6 (ON). Movement of Lrp between proximal and distal sites controls pap pilin transcription and is modulated by PapI and DNA adenine methylase. Here we show that activation of the environmentally responsive CpxAR two-component regulatory system inhibits Pap phase variation by generation of phosphorylated CpxR (CpxR-P). CpxR-P competes with Lrp for binding to both promoter proximal and distal pap DNA binding sites, inhibiting pap transcription in vitro and pili expression in vivo. In contrast to Lrp, CpxR-P is methylation insensitive and does not form DNA methylation patterns in vivo. CpxAR-dependent repression of pap transcription is also observed in response to alkaline growth conditions. These results provide insight into a mechanism for environmental control of epigenetically regulated gene expression.
authors.affiliation: Biomolecular Sciences and Engineering, University of California, Santa Barbara, Santa Barbara, California 93106, USA.
authors.forename: Aaron D
authors.initials: AD
authors.lastname: Hernday
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Braaten
authors.forename: Gina
authors.initials: G
authors.lastname: Broitman-Maduro
authors.forename: Patrick
authors.initials: P
authors.lastname: Engelberts
authors.forename: David A
authors.initials: DA
authors.lastname: Low
mesh_terms: D001426:Bacterial Proteins / Q000302:isolation & purification / Q000378:metabolism*; D001665:Binding Sites; D018983:DNA Footprinting; D004268:DNA-Binding Proteins / Q000378:metabolism*; D044127:Epigenesis, Genetic; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics* / Q000378:metabolism; D010861:Fimbriae, Bacterial / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D005812:Genes, Switch; D006863:Hydrogen-Ion Concentration; D051756:Leucine-Responsive Regulatory Protein; D008954:Models, Biological; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D015265:Site-Specific DNA-Methyltransferase (Adenine-Specific) / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; C497278:Lrp protein, E coli; D014157:Transcription Factors; D051756:Leucine-Responsive Regulatory Protein; C085504:CpxR protein, Bacteria; D015265:Site-Specific DNA-Methyltransferase (Adenine-Specific)