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Updated: Jun 23, 2026
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Biochemical Reconstitution of Steroid Receptor•Hsp90 Protein Complexes and Reactivation of Ligand Binding
Published on: September 21, 2011
DNA binding site sequence directs glucocorticoid receptor structure and activity.
Sebastiaan H Meijsing1, Miles A Pufall, Alex Y So
1Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA.
Science (New York, N.Y.)
|April 18, 2009
Summary
Gene expression is precisely controlled by factors like the glucocorticoid receptor (GR). DNA binding sequences fine-tune GR activity, acting as sequence-specific ligands to regulate target genes.
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- Gene expression requires precise modulation, not just on/off switching.
- The glucocorticoid receptor (GR) binds specific DNA sequences to regulate target genes.
- These DNA binding sites were traditionally considered simple docking sites.
Purpose of the Study:
- To investigate how DNA sequence variations influence glucocorticoid receptor (GR) conformation and function.
- To understand the precise mechanisms of gene expression modulation by GR.
Main Methods:
- Structural assays
- Biochemical assays
- Cell-based assays
Main Results:
- Subtle differences in DNA binding sequences (even single base pairs) alter GR conformation.
- These sequence variations lead to differential regulatory activity of GR.
- GR binding sequences are shown to directly impact receptor conformation and function.
Conclusions:
- DNA acts as a sequence-specific allosteric ligand for the glucocorticoid receptor (GR).
- This allosteric regulation allows GR to tailor its activity for specific target genes.
- The DNA sequence itself plays an active role in modulating gene expression.
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