The mechanism by which DNA adenine methylase and PapI activate the pap epigenetic switch.
The expression of pyelonephritis-associated pili (Pap) in uropathogenic Escherichia coli is epigenetically controlled by a reversible OFF to ON switch. In phase OFF cells, the global regulator Lrp is bound to pap sites proximal to the pilin promoter, whereas in phase ON cells, Lrp is bound to promoter distal sites. We have found that the local regulator PapI increases the affinity of Lrp for the sequence "ACGATC," which contains the target "GATC" site for DNA adenine methylase (Dam) and is present in both promoter proximal and distal sites. Mutational analyses show that methylation of the promoter proximal GATC(prox) site by Dam is required for transition to the phase ON state by specifically blocking PapI-dependent binding of Lrp to promoter proximal sites. Furthermore, our data support the hypothesis that PapI-dependent binding of Lrp to a hemimethylated GATC(dist) site generated by DNA replication is a critical component of the switch mechanism.
Biomolecular Sciences and Engineering, University of California, Santa Barbara, Santa Barbara, CA 93106, USA.
Aaron D
AD
Hernday
Bruce A
BA
Braaten
David A
DA
Low
D001483:Base Sequence / Q000235:genetics; D001665:Binding Sites / Q000235:genetics; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics; D044127:Epigenesis, Genetic / Q000235:genetics*; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics / Q000502:physiology*; D051756:Leucine-Responsive Regulatory Protein; D011401:Promoter Regions, Genetic / Q000235:genetics; D012097:Repressor Proteins / Q000378:metabolism*; D015265:Site-Specific DNA-Methyltransferase (Adenine-Specific) / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; C497278:Lrp protein, E coli; C086707:PapI protein, E coli; D012097:Repressor Proteins; D014157:Transcription Factors; D051756:Leucine-Responsive Regulatory Protein; C058693:Dam methyltransferase; D015265:Site-Specific DNA-Methyltransferase (Adenine-Specific); C499294:dam protein, E coli