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Structural determinants of a glucocorticoid receptor recognition element.
S K Nordeen1, B J Suh, B Kühnel
1Department of Pathology, University of Colorado Health Sciences Center, Denver 80262.
Molecular Endocrinology (Baltimore, Md.)
|December 11, 1990
Summary
This study analyzed mutant glucocorticoid response elements (GREs) to define active GRE features. Results show GREs function as two cooperative half-sites, with specific base pairs and spacing being critical for glucocorticoid receptor binding.
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- Glucocorticoid response elements (GREs) are crucial DNA sequences that regulate gene expression.
- Understanding the precise molecular interactions between GREs and the glucocorticoid receptor is essential for deciphering gene regulation.
Purpose of the Study:
- To define the critical features of an active GRE by analyzing a series of mutant GREs.
- To elucidate the binding mechanism of the glucocorticoid receptor to GREs.
Main Methods:
- Analysis of the relative inducibility of an extensive series of mutant GREs.
- Assessing GRE activity based on glucocorticoid receptor binding.
Main Results:
- Active GREs are composed of two hexamer half-sites, each recognized by a receptor dimer subunit cooperatively.
- Integrity and precise spacing of both half-sites are essential for GRE function.
- Specific base pair positions within the half-site are critical for receptor recognition, while one position shows flexibility.
Conclusions:
- The glucocorticoid receptor recognizes GREs as two separable subelements within each hexamer half-site.
- The DNA-binding domain of the glucocorticoid receptor likely consists of distinct subdomains interacting with these recognition sequence subelements.