Vitamin D-regulated gene expression.

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.