title: OxyR-dependent formation of DNA methylation patterns in OpvABOFF and OpvABON cell lineages of Salmonella enterica.
abstract: Phase variation of the Salmonella enterica opvAB operon generates a bacterial lineage with standard lipopolysaccharide structure (OpvAB(OFF)) and a lineage with shorter O-antigen chains (OpvAB(ON)). Regulation of OpvAB lineage formation is transcriptional, and is controlled by the LysR-type factor OxyR and by DNA adenine methylation. The opvAB regulatory region contains four sites for OxyR binding (OBSA-D), and four methylatable GATC motifs (GATC1-4). OpvAB(OFF) and OpvAB(ON) cell lineages display opposite DNA methylation patterns in the opvAB regulatory region: (i) in the OpvAB(OFF) state, GATC1 and GATC3 are non-methylated, whereas GATC2 and GATC4 are methylated; (ii) in the OpvAB(ON) state, GATC2 and GATC4 are non-methylated, whereas GATC1 and GATC3 are methylated. We provide evidence that such DNA methylation patterns are generated by OxyR binding. The higher stability of the OpvAB(OFF) lineage may be caused by binding of OxyR to sites that are identical to the consensus (OBSA and OBSc), while the sites bound by OxyR in OpvAB(ON) cells (OBSB and OBSD) are not. In support of this view, amelioration of either OBSB or OBSD locks the system in the ON state. We also show that the GATC-binding protein SeqA and the nucleoid protein HU are ancillary factors in opvAB control.
authors.affiliation: Departamento de Genética, Universidad de Sevilla, Facultad de Biología, Apartado 1095, 41080 Sevilla, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Cota
authors.affiliation: Leibniz Institute DSMZ-German Collection of Microorganisms and Cell Cultures, 38124 Braunschweig, Germany German Centre of Infection Research (DZIF), Partner Site Hannover-Braunschweig, 38124 Braunschweig, Germany.
authors.forename: Boyke
authors.initials: B
authors.lastname: Bunk
authors.affiliation: Leibniz Institute DSMZ-German Collection of Microorganisms and Cell Cultures, 38124 Braunschweig, Germany German Centre of Infection Research (DZIF), Partner Site Hannover-Braunschweig, 38124 Braunschweig, Germany.
authors.forename: Cathrin
authors.initials: C
authors.lastname: Spröer
authors.affiliation: Leibniz Institute DSMZ-German Collection of Microorganisms and Cell Cultures, 38124 Braunschweig, Germany German Centre of Infection Research (DZIF), Partner Site Hannover-Braunschweig, 38124 Braunschweig, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Overmann
authors.affiliation: Pacific Biosciences, 1380 Willow Rd, Menlo Park, CA 94025, USA.
authors.forename: Christoph
authors.initials: C
authors.lastname: König
authors.affiliation: Departamento de Genética, Universidad de Sevilla, Facultad de Biología, Apartado 1095, 41080 Sevilla, Spain casadesus@us.es.
authors.forename: Josep
authors.initials: J
authors.lastname: Casadesús
mesh_terms: D000942:Antigens, Bacterial / Q000235:genetics; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D004269:DNA, Bacterial / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial; D019081:O Antigens / Q000235:genetics* / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D012486:Salmonella typhimurium / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D004268:DNA-Binding Proteins; D019081:O Antigens; D014157:Transcription Factors