title: FeON-FeOFF: the Helicobacter pylori Fur regulator commutates iron-responsive transcription by discriminative readout of opposed DNA grooves.
abstract: Most transcriptional regulators bind nucleotide motifs in the major groove, although some are able to recognize molecular determinants conferred by the minor groove of DNA. Here we report a transcriptional commutator switch that exploits the alternative readout of grooves to mediate opposite output regulation for the same input signal. This mechanism accounts for the ability of the Helicobacter pylori Fur regulator to repress the expression of both iron-inducible and iron-repressible genes. When iron is scarce, Fur binds to DNA as a dimer, through the readout of thymine pairs in the major groove, repressing iron-inducible transcription (FeON). Conversely, on iron-repressible elements the metal ion acts as corepressor, inducing Fur multimerization with consequent minor groove readout of AT-rich inverted repeats (FeOFF). Our results provide first evidence for a novel regulatory paradigm, in which the discriminative readout of DNA grooves enables to toggle between the repression of genes in a mutually exclusive manner.
authors: Department of Pharmacy and Biotechnology (FaBiT), University of Bologna, 40126 Bologna, Italy.
authors: Francesca
authors: F
authors: Agriesti
authors: Davide
authors: D
authors: Roncarati
authors: Francesco
authors: F
authors: Musiani
authors: Cristian
authors: C
authors: Del Campo
authors: Mario
authors: M
authors: Iurlaro
authors: Francesca
authors: F
authors: Sparla
authors: Stefano
authors: S
authors: Ciurli
authors: Alberto
authors: A
authors: Danielli
authors: Vincenzo
authors: V
authors: Scarlato
mesh_terms: D000494:Allosteric Regulation; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D001483:Base Sequence; D016384:Consensus Sequence; D004269:DNA, Bacterial / Q000737:chemistry* / Q000378:metabolism; D004214:Distamycins / Q000494:pharmacology; D015964:Gene Expression Regulation, Bacterial; D016480:Helicobacter pylori / Q000235:genetics*; D007501:Iron / Q000378:metabolism*; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D009875:Operator Regions, Genetic; D011485:Protein Binding; D012097:Repressor Proteins / Q000737:chemistry / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial; D004214:Distamycins; D012097:Repressor Proteins; C068477:ferric uptake regulating proteins, bacterial; C030000:stallimycin; D007501:Iron