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EnglishMost 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 transcrip- tional commutator switch that exploits the alternative readout of grooves to mediate opposite output regu- lation 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.
| Titolo: | FeON-FeOFF: the Helicobacter pylori Fur regulator commutates iron-responsive transcription by discriminative readout of opposed DNA grooves |
| Autore/i: | F. Agriesti; RONCARATI, DAVIDE; MUSIANI, FRANCESCO; C. Del Campo; M. Iurlaro; SPARLA, FRANCESCA; CIURLI, STEFANO LUCIANO; DANIELLI, ALBERTO; SCARLATO, VINCENZO |
| Autore/i Unibo: | |
| Anno: | 2014 |
| Rivista: | |
| Digital Object Identifier (DOI): | http://dx.doi.org/10.1093/nar/gkt1258 |
| 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 transcrip- tional commutator switch that exploits the alternative readout of grooves to mediate opposite output regu- lation 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. |
| Data prodotto definitivo in UGOV: | 2013-12-19 17:24:07 |
| Appare nelle tipologie: | 1.01 Articolo in rivista |
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