Article

Allosteric underwinding of DNA is a critical step in positive control of transcription by Hg-MerR.

Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, Illinois 60208-3113.
Nature (impact factor: 36.28). 02/1992; 355(6355):87-9. DOI:10.1038/355087a0 pp.87-9
Source: PubMed

ABSTRACT Positive control of transcription often involves stimulatory protein-protein interactions between regulatory factors and RNA polymerase. Critical steps in the activation process itself are seldom ascribed to protein-DNA distortions. Activator-induced DNA bending is typically assigned a role in binding-site recognition, alterations in DNA loop structures or optimal positioning of the activator for interaction with polymerase. Here we present a transcriptional activation mechanism that does not require a signal-induced DNA bend but rather a receptor-induced untwisting of duplex DNA. The allosterically modulated transcription factor MerR is a repressor and an Hg(II)-responsive activator of bacterial mercury-resistance genes. Escherichia coli RNA polymerase binds to the MerR-promoter complex but cannot proceed to a transcriptionally active open complex until Hg(II) binds to MerR (ref. 6). Chemical nuclease studies show that the activator form, but not the repressor, induces a unique alteration of the helical structure localized at the centre of the DNA-binding site. Data presented here indicate that this Hg-MerR-induced DNA distortion corresponds to a local underwinding of the spacer region of the promoter by about 33 degrees relative to the MerR-operator complex. The magnitude and the direction of the Hg-MerR-induced change in twist angle are consistent with a positive control mechanism involving reorientation of conserved, but suboptimally phased, promoter elements and are consistent with a role for torsional stress in formation of an open complex.

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Keywords

activation process
 
bacterial mercury-resistance genes
 
Chemical nuclease studies
 
duplex DNA
 
Escherichia coli RNA polymerase binds
 
helical structure localized
 
Hg(II)-responsive activator
 
Hg-MerR-induced DNA distortion
 
local underwinding
 
Positive control
 
positive control mechanism
 
promoter elements
 
receptor-induced untwisting
 
regulatory factors
 
RNA polymerase
 
signal-induced DNA
 
spacer region
 
stimulatory protein-protein interactions
 
transcriptional activation mechanism
 
twist angle