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DNA-bend modulation in a repressor-to-activator switching mechanism
A Z Ansari1, J E Bradner, T V O'Halloran
1Department of Chemistry, Northwestern University, Evanston, Illinois 60208-3113.
Nature
|March 23, 1995
Summary
The transcription factor MerR regulates bacterial mercury-detoxification genes by altering DNA structure. It acts as a repressor until mercuric ions bind, converting it to an activator that remodels the promoter for gene expression.
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- Transcriptional regulation is influenced by DNA structure.
- Activator proteins that distort DNA but lack activation domains are of recent interest.
- The transcription factor MerR's role in regulating bacterial mercury-detoxification genes is under investigation.
Purpose of the Study:
- To elucidate the mechanism by which MerR mediates both transcriptional repression and activation.
- To investigate the role of DNA structure modulation by MerR in gene regulation.
- To understand how mercuric ions alter MerR's function.
Main Methods:
- DNase I sensitivity assays to identify DNA bending loci.
- Analysis of MerR-DNA interactions in the presence and absence of mercuric ions.
- Characterization of RNA polymerase complex formation and activation at the PT promoter.
Main Results:
- MerR binds between the -10 and -35 promoter elements, forming an inactive complex with RNA polymerase.
- Mercuric ion binding induces a conformational change in MerR (Hg-MerR), converting it to an activator.
- MerR bends DNA at two loci; Hg-MerR relaxes these bends and untwists the operator, remodeling the promoter.
Conclusions:
- MerR functions as a stereospecific modulator of DNA structure to control gene transcription.
- The conformational change in MerR upon mercuric ion binding is crucial for activating transcription.
- MerR-induced DNA remodeling creates a more favorable template for poised RNA polymerase, enabling gene expression.