title: Dual-function regulators: the cAMP receptor protein and the CytR regulator can act either to repress or to activate transcription depending on the context.
abstract: Studies of gene regulation have revealed that several transcriptional regulators can switch between activator and repressor depending upon both the promoter and the cellular context. A relatively simple prokaryotic example is illustrated by the Escherichia coli CytR regulon. In this system, the cAMP receptor protein (CRP) assists the binding of RNA polymerase as well as a specific negative regulator, CytR. Thus, CRP functions either as an activator or as a corepressor. Here we show that, depending on promoter architecture, the CRP/CytR nucleoprotein complex has opposite effects on transcription. When acting from a site close to the DNA target for RNA polymerase, CytR interacts with CRP to repress transcription, whereas an interaction with CRP from appropriately positioned upstream binding sites can result in formation of a huge preinitiation complex and transcriptional activation. Based on recent results about CRP-mediated regulation of transcription initiation and the finding that CRP possesses discrete surface-exposed patches for protein-protein interaction with RNA polymerase and CytR, a molecular model for this dual regulation is discussed.
authors.affiliation: Department of Molecular Biology, Odense University, Denmark.
authors.forename: P B
authors.initials: PB
authors.lastname: Rasmussen
authors.forename: B
authors.initials: B
authors.lastname: Holst
authors.forename: P
authors.initials: P
authors.lastname: Valentin-Hansen
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D002373:Cyclic AMP Receptor Protein / Q000737:chemistry / Q000378:metabolism*; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins; D006639:Histidine; D008961:Models, Structural; D016296:Mutagenesis; D009690:Nucleic Acid Conformation; D011392:Proline; D011401:Promoter Regions, Genetic; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014633:Valine; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D002373:Cyclic AMP Receptor Protein; C048425:CytR protein, E coli; D029968:Escherichia coli Proteins; D011994:Recombinant Proteins; D012097:Repressor Proteins; D006639:Histidine; D004247:DNA; D011392:Proline; D012321:DNA-Directed RNA Polymerases; D001616:beta-Galactosidase; D014633:Valine