1,25-Dihydroxyvitamin D3 Controls a Cohort of Vitamin D Receptor Target Genes in the Proximal Intestine That Is Enriched for Calcium-regulating Components
| Autor: | Seong Min Lee, Lori A. Plum, Erin M. Riley, J. Wesley Pike, Hector F. DeLuca, Mark B. Meyer, Nancy A. Benkusky |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Vitamin medicine.medical_specialty TRPV6 25-Hydroxyvitamin D3 1-alpha-hydroxylase chemistry.chemical_element Biology Calcium Biochemistry Calcitriol receptor Mice chemistry.chemical_compound Intestinal mucosa Internal medicine medicine Vitamin D and neurology Animals Gene Regulatory Networks Gene Regulation Intestinal Mucosa Vitamin D Molecular Biology 25-Hydroxyvitamin D3 1-alpha-Hydroxylase Calcium metabolism Vitamins Cell Biology Intestines Mice Inbred C57BL Endocrinology Gene Expression Regulation chemistry Receptors Calcitriol Female Gene Deletion |
| Zdroj: | Journal of Biological Chemistry. 290:18199-18215 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m115.665794 |
| Popis: | 1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) plays an integral role in calcium homeostasis in higher organisms through its actions in the intestine, kidney, and skeleton. Interestingly, although several intestinal genes are known to play a contributory role in calcium homeostasis, the entire caste of key components remains to be identified. To examine this issue, Cyp27b1 null mice on either a normal or a high calcium/phosphate-containing rescue diet were treated with vehicle or 1,25(OH)2D3 and evaluated 6 h later. RNA samples from the duodena were then subjected to RNA sequence analysis, and the data were analyzed bioinformatically. 1,25(OH)2D3 altered expression of large collections of genes in animals under either dietary condition. 45 genes were found common to both 1,25(OH)2D3-treated groups and were composed of genes previously linked to intestinal calcium uptake, including S100g, Trpv6, Atp2b1, and Cldn2 as well as others. An additional distinct network of 56 genes was regulated exclusively by diet. We then conducted a ChIP sequence analysis of binding sites for the vitamin D receptor (VDR) across the proximal intestine in vitamin D-sufficient normal mice treated with vehicle or 1,25(OH)2D3. The residual VDR cistrome was composed of 4617 sites, which was increased almost 4-fold following hormone treatment. Interestingly, the majority of the genes regulated by 1,25(OH)2D3 in each diet group as well as those found in common in both groups contained frequent VDR sites that likely regulated their expression. This study revealed a global network of genes in the intestine that both represent direct targets of vitamin D action in mice and are involved in calcium absorption. |
| Databáze: | OpenAIRE |
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