Gene Regulation
A kidney-specific genetic control module in mice governs endocrine regulation of the cytochrome P450 gene Cyp27b1 essential for vitamin D3 activation
The vitamin D endocrine system regulates mineral homeostasis through its activities in the intestine, kidney, and bone. Terminal activation of vitamin D3 to its hormonal form, 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3), occurs in the kidney via the cytochrome P450 enzyme CYP27B1. Despite its importance in vitamin D metabolism, the molecular mechanisms underlying the regulation of the gene for this enzyme, Cyp27b1, are unknown. Here, we identified a kidney-specific control module governed by a renal cell-specific chromatin structure located distal to Cyp27b1 that mediates unique basal and parathyroid hormone (PTH)-, fibroblast growth factor 23 (FGF23)-, and 1,25(OH)2D3-mediated regulation of Cyp27b1 expression.Mechanisms of Enhancer-mediated Hormonal Control of Vitamin D Receptor Gene Expression in Target Cells
Background: Expression of the vitamin D receptor (VDR) is regulated by hormones in a tissue-specific manner.Results: Enhancers potentially involved in the regulation of VDR expression were characterized in mouse tissues in vivo.Conclusion: Regulation of VDR expression is mediated by tissue-specific enhancers.Significance: Defining potential regulatory regions allows us to predict VDR expression in target tissues.1,25-Dihydroxyvitamin D3 Controls a Cohort of Vitamin D Receptor Target Genes in the Proximal Intestine That Is Enriched for Calcium-regulating Components
Background Vitamin D3 regulates intestinal calcium absorption to maintain mineral homeostasis. Results Genome-wide analyses reveal vitamin D3 target genes and their regulatory components in intestine. Conclusion A gene network involved in vitamin D3-mediated calcium uptake in the intestine is defined. Significance The network of genes provides a basis for understanding molecular mechanisms of vitamin D3-mediated active calcium transport in the intestine.
