Dynamics of 1α,25-dihydroxyvitamin D3-dependent chromatin accessibility of early vitamin D receptor target genes

2013 ◽  
Vol 1829 (12) ◽  
pp. 1266-1275 ◽  
Author(s):  
Sabine Seuter ◽  
Petri Pehkonen ◽  
Sami Heikkinen ◽  
Carsten Carlberg
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Target Genes ◽  
Chromatin Accessibility ◽  
Dihydroxyvitamin D3

Temporal changes in tissue 1α,25-dihydroxyvitamin D3, vitamin D receptor target genes, and calcium and PTH levels after 1,25(OH)2D3 treatment in mice

2013 ◽  
Vol 304 (9) ◽  
pp. E977-E989 ◽  
Author(s):  
Edwin C. Y. Chow ◽  
Holly P. Quach ◽  
Reinhold Vieth ◽  
K. Sandy Pang
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Calcium Ion ◽  
Target Genes ◽  
Feedback Regulation ◽  
Plasma Calcium ◽  
Dihydroxyvitamin D3 ◽  
Dihydroxyvitamin D ◽  
Temporal Correlations ◽  
Temporal Profiles

The vitamin D receptor (VDR) maintains a balance of plasma calcium and 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3], its natural active ligand, by directly regulating the calcium ion channel (TRPV6) and degradation enzyme (CYP24A1), and indirectly regulating the parathyroid hormone (PTH) for feedback regulation of the synthetic enzyme CYP27B1. Studies that examined the intricate relationships between plasma and tissue 1,25(OH)2D3 levels and changes in VDR target genes and plasma calcium and PTH are virtually nonexistent. In this study, we investigated temporal correlations between tissue 1,25(OH)2D3 concentrations and VDR target genes in ileum and kidney and plasma calcium and PTH concentrations in response to 1,25(OH)2D3 treatment in mice (2.5 μg/kg ip, singly or q2d × 4). After a single ip dose, plasma 1,25(OH)2D3 peaked at ∼0.5 h and then decayed biexponentially, falling below basal levels after 24 h and then returning to baseline after 8 days. Upon repetitive ip dosing, plasma, ileal, renal, and bone 1,25(OH)2D3 concentrations rose and decayed in unison. Temporal profiles showed increased expressions of ileal Cyp24a1 and renal Cyp24a1, Mdr1/P-gp, and VDR but decreased renal Cyp27b1 mRNA after a time delay in VDR activation. Increased plasma calcium and attenuated PTH levels and increased ileal and renal Trpv6 expression paralleled the changes in tissue 1,25(OH)2D3 concentrations. Gene changes in the kidney were more sustained than those in intestine, but the magnitudes of change for Cyp24a1 and Trpv6 were lower than those in intestine. The data revealed that 1,25(OH)2D3 equilibrates with tissues rapidly, and VDR target genes respond quickly to exogenously administered 1,25(OH)2D3.

scholarly journals Repression of basal transcription by vitamin D receptor: evidence for interaction of unliganded vitamin D receptor with two receptor interaction domains in RIP13delta1

1998 ◽  
Vol 20 (3) ◽  
pp. 327-335 ◽  
Author(s):  
PP Dwivedi ◽  
GE Muscat ◽  
PJ Bailey ◽  
JL Omdahl ◽  
BK May
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Target Genes ◽  
Dominant Negative ◽  
Receptor Interaction ◽  
Kidney Cells ◽  
Basal Transcription ◽  
Dihydroxyvitamin D3 ◽  
Promoter Construct ◽  
Interaction Domains

Repression of basal transcription of a 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) responsive 25-hydroxyvitamin D3-24-hydroxylase (CYP24) promoter construct as observed in kidney cells in the absence of ligand and this repression was dependent on a functional vitamin D response element (VDRE). Basal repression was also seen with a construct where a consensus DR-3-type VDRE was fused to the thymidine kinase promoter. Expression of a dominant negative vitamin D receptor (VDR) isoform that strongly bound to the VDRE motif in the CYP24 promoter ablated basal repression. This VDR isoform lacked sequence in the hinge- and ligand-binding domains implicating one or both of these domains in basal repression. It is well known that thyroid hormone and retinoic acid receptors silence basal transcription of target genes in the absence of ligands and this repressor function can be mediated by the nuclear receptor corepressor N-CoR. Two variants of N-CoR have been described, RIP13a and RIP13delta1. N-CoR and the variants contain two receptor interaction domains, ID-I and ID-II, which are identical except region ID-II in RIP13delta1 has an internal deletion. We have used the mammalian two hybrid system to investigate whether VDR, in the absence of ligand 1,25-(OH)2D3, can interact with these domains. The data showed that unliganded VDR does not interact with either ID-I or ID-II from RIP13a and RIP13delta1, but does interact strongly with a composite domain of ID-I and ID-II from RIP13delta1 (but not from RIP13a) and this strong interaction is abrogated in the presence of ligand. This finding implicates RIP13delta1 in VDR-dependent basal repression of the promoter constructs under investigation. However, over-expression of RIP13delta1 in kidney cell lines did not alter basal expression of the CYP24 promoter construct. It is concluded that either the level of endogenous RIP13delta1 in these kidney cells permits maximal repression or that repression occurs by a mechanism that is independent of RIP13delta1. Alternatively, repression may be dependent on RIP13delta1 but requires an additional cofactor that is limiting in these cells.

scholarly journals The 1,25(OH)2D3-Regulated Transcription Factor MN1 Stimulates Vitamin D Receptor-Mediated Transcription and Inhibits Osteoblastic Cell Proliferation

2005 ◽  
Vol 19 (9) ◽  
pp. 2234-2244 ◽  
Author(s):  
Amelia L. M. Sutton ◽  
Xiaoxue Zhang ◽  
Tara I. Ellison ◽  
Paul N. MacDonald
Keyword(s):  
Vitamin D ◽  
Cell Proliferation ◽  
Vitamin D Receptor ◽  
Target Genes ◽  
Ion Homeostasis ◽  
Endocrine System ◽  
Osteoblastic Cells ◽  
Osteoblastic Cell ◽  
Dihydroxyvitamin D3 ◽  
And Function

Abstract The vitamin D endocrine system is essential for maintaining mineral ion homeostasis and preserving bone density. The most bioactive form of vitamin D, 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] elicits its effects by binding to the vitamin D receptor (VDR) and regulating the transcription of target genes. In osteoblasts, the bone-forming cells of the skeleton, 1,25-(OH)2D3 regulates cell proliferation, differentiation, and mineralization of the extracellular matrix. Despite these well-characterized biological functions, relatively few 1,25-(OH)2D3 target genes have been described in osteoblasts. In this study, we characterize the regulation and function of MN1, a novel 1,25-(OH)2D3-induced gene in osteoblastic cells. MN1 is a nuclear protein first identified as a gene disrupted in some meningiomas and leukemias. Our studies demonstrate that MN1 preferentially stimulates VDR-mediated transcription through its ligand-binding domain and synergizes with the steroid receptor coactivator family of coactivators. Furthermore, forced expression of MN1 in osteoblastic cells results in a profound decrease in cell proliferation by slowing S-phase entry, suggesting that MN1 is an antiproliferative factor that may mediate 1,25-(OH)2D3-dependent inhibition of cell growth. Collectively, these data indicate that MN1 is a 1,25-(OH)2D3-induced VDR coactivator that also may have critical roles in modulating osteoblast proliferation.

scholarly journals Nutraceuticals Derived From Pomegranate Selectively Enhance Vitamin D Receptor Signaling to Amplify Key Vitamin D Target Genes

2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Sarah Livingston ◽  
Daniel Lucas ◽  
Marya S. Sabir ◽  
Sanchita Mallick ◽  
Hespera Purdin ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Target Genes ◽  
Receptor Signaling

scholarly journals Genome-wide effects of chromatin on vitamin D signaling

2020 ◽  
Vol 64 (4) ◽  
pp. R45-R56 ◽  
Author(s):  
Andrea Hanel ◽  
Henna-Riikka Malmberg ◽  
Carsten Carlberg
Keyword(s):  
Vitamin D ◽  
Binding Sites ◽  
Target Genes ◽  
Chromatin Accessibility ◽  
Transcription Start Sites ◽  
Dihydroxyvitamin D ◽  
Genome Wide ◽  
Spatio Temporal ◽  
Vitamin D Signaling ◽  
The Impact

Molecular endocrinology of vitamin D is based on the activation of the transcription factor vitamin D receptor (VDR) by the vitamin D metabolite 1α,25-dihydroxyvitamin D3. This nuclear vitamin D-sensing process causes epigenome-wide effects, such as changes in chromatin accessibility as well as in the contact of VDR and its supporting pioneer factors with thousands of genomic binding sites, referred to as vitamin D response elements. VDR binding enhancer regions loop to transcription start sites of hundreds of vitamin D target genes resulting in changes of their expression. Thus, vitamin D signaling is based on epigenome- and transcriptome-wide shifts in VDR-expressing tissues. Monocytes are the most responsive cell type of the immune system and serve as a paradigm for uncovering the chromatin model of vitamin D signaling. In this review, an alternative approach for selecting vitamin D target genes is presented, which are most relevant for understanding the impact of vitamin D endocrinology on innate immunity. Different scenarios of the regulation of primary upregulated vitamin D target genes are presented, in which vitamin D-driven super-enhancers comprise a cluster of persistent (constant) and/or inducible (transient) VDR-binding sites. In conclusion, the spatio-temporal VDR binding in the context of chromatin is most critical for the regulation of vitamin D target genes.

Vitamin D receptor in IMR-90 human fibroblasts and antiproliferative effect of 1,25-dihydroxyvitamin D3

IUBMB Life ◽  
1997 ◽  
Vol 43 (6) ◽  
pp. 1173-1181 ◽  
Author(s):  
M. Stio ◽  
A. Celli ◽  
B. Lunghi ◽  
G. Raugei ◽  
A. Modesti ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Human Fibroblasts ◽  
Antiproliferative Effect ◽  
Dihydroxyvitamin D3 ◽  
1,25 Dihydroxyvitamin D3

Molecular network of chromatin immunoprecipitation followed by deep sequencing-based vitamin D receptor target genes

2013 ◽  
Vol 19 (8) ◽  
pp. 1035-1045 ◽  
Author(s):  
Jun-ichi Satoh ◽  
Hiroko Tabunoki
Keyword(s):  
Multiple Sclerosis ◽  
Vitamin D ◽  
Vitamin D Receptor ◽  
Deep Sequencing ◽  
Immune Cells ◽  
Chromatin Immunoprecipitation ◽  
Target Genes ◽  
Molecular Network ◽  
Genome Wide

Background: Vitamin D is a liposoluble vitamin essential for calcium metabolism. The ligand-bound vitamin D receptor (VDR), heterodimerized with retinoid X receptor, interacts with vitamin D response elements (VDREs) to regulate gene expression. Vitamin D deficiency due to insufficient sunlight exposure confers an increased risk for multiple sclerosis (MS). Objective: To study a protective role of vitamin D in multiple sclerosis (MS), it is important to characterize the global molecular network of VDR target genes (VDRTGs) in immune cells. Methods: We identified genome-wide VDRTGs collectively from two distinct chromatin immunoprecipitation followed by deep sequencing (ChIP-Seq) datasets of VDR-binding sites derived from calcitriol-treated human cells of B cell and monocyte origins. We mapped short reads of next generation sequencing (NGS) data on hg19 with Bowtie, detected the peaks with Model-based Analysis of ChIP-Seq (MACS), and identified genomic locations by GenomeJack, a novel genome viewer for NGS platforms. Results: We found 2997 stringent peaks distributed on protein-coding genes, chiefly located in the promoter and the intron on VDRE DR3 sequences. However, the corresponding transcriptome data verified calcitriol-induced upregulation of only a small set of VDRTGs. The molecular network of 1541 calcitriol-responsive VDRTGs showed a significant relationship with leukocyte transendothelial migration, Fcγ receptor-mediated phagocytosis, and transcriptional regulation by VDR, suggesting a pivotal role of genome-wide VDRTGs in immune regulation. Conclusion: These results suggest the working hypothesis that persistent deficiency of vitamin D might perturb the complex network of VDRTGs in immune cells, being responsible for induction of an autoimmune response causative for MS.

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