Annotation inferences using phylogenetic trees
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
Cif is negatively regulated by the TetR family repressor CifR.
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PA2931 (renamed CifR) binds the promoter region upstream of the cif operon and represses cif; the epoxide epibromohydrin disrupts the protein-DNA interaction in vitro and induces cif expression.
"We show that the predicted TetR family transcriptional repressor encoded by the PA2931 gene, which is immediately adjacent to and divergently transcribed from the cif-containing, three-gene operon, negatively regulates cif gene expression by binding to the promoter region immediately upstream of the cif-containing operon."
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Clinical isolates with high cif expression have reduced cifR expression.
"Finally, we demonstrate that P. aeruginosa strains isolated from cystic fibrosis patient sputum with increased cif gene expression are impaired for the expression of the cifR gene."
Epoxide-mediated CifR repression of cif gene expression utilizes two binding sites in Pseudomonas aeruginosa.
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Two 27-bp CifR operators in the cifR-morB intergenic region overlap the -10 and +1 elements of both divergent promoters; mutating them abolishes binding in vitro and increases cif and cifR transcription in vivo.
"Mutagenesis of these binding sites resulted in a loss of DNA binding in vitro, and mutation of one of these sites in vivo resulted in an increase in transcription of both the cif and cifR genes."
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CifR binds at two operators, unlike single-site TetR-family repressors.
"However, these repressors have all been shown to bind at a single site to mediate repression of the operon as either a dimer or a dimer of dimers ( 4 , 33 , 35 ), whereas CifR binds at two distinct operators, separated by 28 bp, to control the expression of divergently transcribed loci."
Molecular basis for the transcriptional regulation of an epoxide-based virulence circuit in Pseudomonas aeruginosa.
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Structures of free CifR and of the CifR-operator complex show one dimer per operator, with the N-terminal extension in the DNA minor groove; Cys107 is required for epoxide sensing and DNA release.
"We also determined that cysteine residue Cys107 is critical for epoxide sensing and DNA release."
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Epibromohydrin releases CifR from the intergenic operators, permitting transcription.
"Furthermore, EBH disrupts CifR binding to the intergenic promoter region, permitting transcription of cifR and the three divergently transcribed genes including cif ( 16 , 18 ) (Figure 1; bottom row)."