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All natural DR3-type vitamin D response elements show a similar functionality in vitro
1Institut für Physiologische Chemie I and Biomedizinisches Forschungszentrum, Heinrich-Heine-Universität, Postfach 10 10 07, D-40001 Düsseldorf, Germany.
The Biochemical Journal
|November 22, 2000
Summary
The vitamin D(3) receptor (VDR) and retinoid X receptor (RXR) bind to vitamin D response elements (VDREs). VDREs were classified by their VDR-RXR binding affinity, revealing it as the key factor in gene regulation.
Area of Science:
- Molecular Endocrinology
- Genetics
- Biochemistry
Background:
- The vitamin D(3) receptor (VDR) forms heterodimers with the retinoid X receptor (RXR).
- This complex binds to specific DNA sequences known as vitamin D response elements (VDREs), particularly DR3-type elements.
- Understanding VDREs is crucial for deciphering the genomic actions of vitamin D.
Purpose of the Study:
- To compare and classify all known natural DR3-type VDREs.
- To analyze their complex formation with VDR-RXR heterodimers and stabilization of conformations.
- To identify the primary factors governing VDR-RXR binding to VDREs.
Main Methods:
- Classification of natural DR3-type VDREs based on VDR-RXR heterodimer complex formation.
- Assessment of VDREs' ability to stabilize VDR-RXR heterodimer conformations.
- Determination of ligand sensitivity and interactions with co-activators/co-repressors.
Main Results:
- DR3-type VDREs were categorized into three classes based on their affinity for VDR-RXR heterodimers.
- Ligand sensitivity for complex formation and stabilization was observed at 0.1 nM.
- No significant differences were found in interactions with co-activator SRC-1 or co-repressor NCoR.
Conclusions:
- VDRE binding affinity for VDR-RXR heterodimers is the major discriminating factor among natural DR3-type VDREs.
- This finding aids in understanding DR3-type VDRE-mediated gene regulation.
- DR3-type VDREs alone are insufficient to explain the diverse genomic effects of vitamin D.