Allosteric transcriptional regulation via changes in the overall topology of the core promoter

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Science  21 Aug 2015:
Vol. 349, Issue 6250, pp. 877-881
DOI: 10.1126/science.aaa9809

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Transcription factor shape-shifts DNA

Controlling when a gene is expressed or repressed is vital for cellular metabolism and development. In Escherichia coli, a copper-sensing transcription factor, CueR, can repress or activate expression when bound at exactly the same site in the gene promoter. Philips et al. used x-ray crystallography to show that CueR dramatically changes the topology of the DNA upon binding copper but does not affect protein-DNA contacts. The DNA shape change allows RNA polymerase to bind the promoter and transcribe the gene.

Science, this issue p. 877


Many transcriptional activators act at a distance from core promoter elements and work by recruiting RNA polymerase through protein-protein interactions. We show here how the prokaryotic regulatory protein CueR both represses and activates transcription by differentially modulating local DNA structure within the promoter. Structural studies reveal that the repressor state slightly bends the promoter DNA, precluding optimal RNA polymerase-promoter recognition. Upon binding a metal ion in the allosteric site, CueR switches into an activator conformation. It maintains all protein-DNA contacts but introduces torsional stresses that kink and undertwist the promoter, stabilizing an A-form DNA–like conformation. These factors switch on and off transcription by exerting dynamic control of DNA stereochemistry, reshaping the core promoter and making it a better or worse substrate for polymerase.

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