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Vitamin D-regulated gene expression
1Department of Biochemistry, University of Wisconsin-Madison 53706.
Abstract:
The major emphasis of this review is on the molecular events that occur in target tissues when stimulated by 1,25-dihydroxyvitamin D3. The vitamin D receptor is a 55,000-kDa protein whose domains have been described roughly for human and rat. A single receptor appears to carry out all of the known functions of vitamin D and is likely a nucleoprotein. The receptor binds to vitamin D response elements found in the promoter region of responsive genes. An accessory protein is required for the binding of the receptor to these response elements. The accessory protein has a molecular weight of approximately 62,000 kDa but has not been cloned. The response elements are two repeat sequences separated by three bases. A negative response element is known for the parathyroid gene and is a single arm homologous to one arm of the osteopontin response element. Phosphorylation in the ligand binding domain of the receptor follows binding of 1,25-(OH)2D3. The receptor then becomes transcriptively active and interacts with other transcription factors to bring about gene expression. It is unknown, if following phosphorylation, the ligand is released, and final proof that the phosphorylated receptor is the transcriptively active form of the protein is not yet available.
Insights
This review details how vitamin D receptor (VDR) interacts with DNA to regulate gene expression. It highlights the VDR
Area of Science:
- Molecular Biology
- Endocrinology
- Genetics
Background:
- Vitamin D is a crucial hormone regulating calcium homeostasis and cellular processes.
- The biological actions of vitamin D are mediated by the vitamin D receptor (VDR).
- Understanding VDR's molecular interactions is key to deciphering vitamin D's physiological roles.
Purpose of the Study:
- To review the molecular mechanisms of vitamin D action at the target tissue level.
- To elucidate the structure and function of the vitamin D receptor (VDR).
- To describe the interaction of VDR with DNA and accessory proteins in gene regulation.
Main Methods:
- Review of existing literature on vitamin D receptor (VDR) structure and function.
- Analysis of molecular events following 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) stimulation.
- Examination of VDR binding to vitamin D response elements (VDREs) and accessory proteins.
Main Results:
- The vitamin D receptor (VDR) is a 55-kDa nucleoprotein that binds to specific DNA sequences (VDREs).
- An accessory protein (approx. 62 kDa) is required for VDR binding to VDREs.
- 1,25-(OH)2D3 binding induces VDR phosphorylation, leading to transcriptional activation.
Conclusions:
- The vitamin D receptor (VDR) acts as a ligand-dependent transcription factor.
- VDR's interaction with DNA and accessory proteins is critical for gene expression.
- Further research is needed to confirm the role of phosphorylation and ligand release in VDR activity.