A new mechanism of transcriptional regulation: release of an activator triggered by small molecule binding

Cell. 1992 Aug 21;70(4):671-9. doi: 10.1016/0092-8674(92)90435-f.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acyl Coenzyme A / pharmacology
  • Bacterial Proteins / metabolism*
  • Base Sequence
  • Binding, Competitive / drug effects
  • Escherichia coli / genetics*
  • Fatty Acids / pharmacology*
  • Gene Expression Regulation
  • Gene Expression Regulation, Bacterial
  • Molecular Sequence Data
  • Repressor Proteins*
  • Transcription, Genetic / drug effects*


  • Acyl Coenzyme A
  • Bacterial Proteins
  • FadR protein, Bacteria
  • Fatty Acids
  • Repressor Proteins

Associated data

  • GENBANK/J03186
  • GENBANK/L05499
  • GENBANK/M87278
  • GENBANK/M94264
  • GENBANK/M97694
  • GENBANK/S72766
  • GENBANK/S72767
  • GENBANK/S72768
  • GENBANK/S72769
  • GENBANK/S72771