Abstract
Although the cytochrome P450 CYP27B1 plays a critical role in vitamin D biology, the molecular mechanisms involved in regulation of CYP27B1 have remained undefined. A new study has identified a kidney-specific control module distal to the Cyp27b1 gene that mediates the basal activity and hormonal regulation of Cyp27b1 This work provides a novel mechanism indicating differential regulation of Cyp27b1 in renal and non-renal cells and has implications for vitamin D biology in multiple sclerosis and perhaps other autoimmune diseases as well.
Highlights
Vitamin D is critical for calcium homeostasis and is required for the development and maintenance of skeletal integrity
In addition to 1,25(OH)2D3, the phosphaturic factor fibroblast growth factor 23 (FGF23), which acts as an endocrine factor, suppresses expression of renal CYP27B1 [1, 2] (Fig. 1)
The authors found regions of DNA that mediate parathyroid hormone (PTH) induction and 1,25(OH)2D3 and FGF23 suppression of renal Cyp27b1 expression located in selected introns of the nearby Mettl1 and Mettl21b genes
Summary
Vitamin D is critical for calcium homeostasis and is required for the development and maintenance of skeletal integrity. That controls basal and hormone-regulated expression of Cyp27b1. Meyer et al [4] identified, through ChIP-seq analysis, a genomic region distal to Cyp27b1 as a potential control module to explain the regulation observed.
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