A new mechanism of transcriptional regulation: release of an activator triggered by small molecule binding.
The FadR protein of E. coli activates transcription of the fabA gene, a key enzyme of fatty acid synthesis. We report that FadR binds to a DNA sequence positioned at -40 relative to the start site of the FadR-regulated fabA transcript (the location favored by positive activators). This binding was found to be specifically antagonized by long chain acyl-CoAs. The chain length specificity of the disassociation of the FadR-DNA complex by acyl-CoAs observed in vitro reflects that seen in the repression of fabA transcription observed upon addition of fatty acids to bacterial cultures. Acyl-CoA antagonism of FadR-DNA interactions is readily reversible. These data indicate that repression of fabA transcription by fatty acids is the first reported example of a repression system mediated by positive control.
Henry
M F
MF
Department of Microbiology, University of Illinois, Urbana 61801.
Cronan
J E
JE
D000214:Acyl Coenzyme A / Q000494:pharmacology; D001426:Bacterial Proteins / Q000378:metabolism*; D001483:Base Sequence; D001667:Binding, Competitive / Q000187:drug effects; D004926:Escherichia coli / Q000235:genetics*; D005227:Fatty Acids / Q000494:pharmacology*; D005786:Gene Expression Regulation; D015964:Gene Expression Regulation, Bacterial; D008969:Molecular Sequence Data; D012097:Repressor Proteins; D014158:Transcription, Genetic / Q000187:drug effects*
D000214:Acyl Coenzyme A; D001426:Bacterial Proteins; C057119:FadR protein, Bacteria; D005227:Fatty Acids; D012097:Repressor Proteins