FeON-FeOFF: the Helicobacter pylori Fur regulator commutates iron-responsive transcription by discriminative readout of opposed DNA grooves

Francesca Agriesti, Davide Roncarati, Francesco Musiani, Cristian Del Campo, Mario Iurlaro, Francesca Sparla, Stefano Ciurli, Alberto Danielli, Vincenzo Scarlato

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)3138-3151
Number of pages14
JournalNucleic Acids Research
Volume42
Issue number5
DOIs
Publication statusPublished - 2014

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ASJC Scopus subject areas

  • Genetics

Cite this

Agriesti, F., Roncarati, D., Musiani, F., Del Campo, C., Iurlaro, M., Sparla, F., Ciurli, S., Danielli, A., & Scarlato, V. (2014). FeON-FeOFF: the Helicobacter pylori Fur regulator commutates iron-responsive transcription by discriminative readout of opposed DNA grooves. Nucleic Acids Research, 42(5), 3138-3151. https://doi.org/10.1093/nar/gkt1258