scholarly journals In Silico Analysis of Regulatory Elements of the Vitamin D Receptor

2020 ◽  
Vol 17 (2) ◽  
pp. 0463
Author(s):  
Shirin Farivar ◽  
Roya Amirinejad ◽  
Bahar Naghavi gargari ◽  
Seyedeh Batool Hassani ◽  
Zeinab Shirvani farsani
Keyword(s):  
Vitamin D ◽  
Transcription Factor ◽  
Vitamin D Receptor ◽  
Protein Interactions ◽  
Molecular Mechanisms ◽  
Cpg Islands ◽  
In Silico Analysis ◽  
Regulatory Elements ◽  
Protein Protein Interactions ◽  
Vdr Gene

Vitamin D receptor (VDR) is a nuclear transcription factor that controls gene expression. Its impaired expression was found to be related to different diseases. VDR also acts as a regulator of different pathways including differentiation, inflammation, calcium and phosphate absorption, etc. but there is no sufficient knowledge about the regulation of the gene itself. Therefore, a better understanding of the genetic and epigenetic factors regulating the VDR may facilitate the improvement of strategies for the prevention and treatment of diseases associated with dysregulation of VDR. In the present investigation, a set of databases and methods were used to identify putative functional elements in the VDR locus. Histone modifications, CpG Islands, epigenetic marks at VDR locus were indicated. In addition, repeated sequences, enhancers, insulators, transcription factor binding sites and targets of the VDR gene, as well as protein-protein interactions with bioinformatics tools, were reported. Some of these genetic elements had overlapped with CpG Islands. These results revealed important new insight into the molecular mechanisms of the VDR gene regulation in human cells and tissues.

Functional characterization of WT1 binding sites within the human vitamin D receptor gene promoter

2001 ◽  
Vol 7 (2) ◽  
pp. 187-200 ◽  
Author(s):  
TAE HO LEE ◽  
JERRY PELLETIER
Keyword(s):  
Gene Expression ◽  
Vitamin D ◽  
Transcription Factor ◽  
Vitamin D Receptor ◽  
Binding Sites ◽  
Wilms Tumor ◽  
Cdna Array ◽  
Transcriptional Level ◽  
Vdr Gene ◽  
Downstream Target

The Wilms’ tumor suppressor gene, wt1, encodes a zinc finger transcription factor that can regulate gene expression. It plays an essential role in tumorigenesis, kidney differentiation, and urogenital development. To identify WT1 downstream targets, gene expression profiling was conducted using a cDNA array hybridization approach. We confirm herein that the human vitamin D receptor (VDR), a ligand-activated transcription factor, is a WT1 downstream target. Nuclear run on experiments demonstrated that the effect of WT1 on VDR expression is at the transcriptional level. Transient transfection assays, deletion mutagenesis, electrophoretic mobility shift assays, and chromatin immunoprecipitation assays suggest that, although WT1 is presented with a possibility of three binding sites within the VDR promoter, activation of the human VDR gene appears to occur through a single site. This site differs from a previously identified WT1-responsive site in the murine VDR promoter (Maurer U, Jehan F, Englert C, Hübinger G, Weidmann E, DeLucas HF, and Bergmann L. J Biol Chem 276: 3727–3732, 2001). We also show that the products of a Denys-Drash syndrome allele of wt1 inhibit WT1-mediated transactivation of the human VDR promoter. Our results indicate that the human VDR gene is a downstream target of WT1 and may be regulated differently than its murine counterpart.

scholarly journals Functional Diversification of Vitamin D Receptor Paralogs in Teleost Fish After a Whole Genome Duplication Event

Endocrinology ◽  
2014 ◽  
Vol 155 (12) ◽  
pp. 4641-4654 ◽  
Author(s):  
Erin M. Kollitz ◽  
Mary Beth Hawkins ◽  
G. Kerr Whitfield ◽  
Seth W. Kullman
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Protein Interactions ◽  
Whole Genome Duplication ◽  
Genome Duplication ◽  
Genetic Material ◽  
Whole Genome ◽  
Protein Protein Interactions ◽  
Evolutionary Forces ◽  
Functional Differences

The diversity and success of teleost fishes (Actinopterygii) has been attributed to three successive rounds of whole-genome duplication (WGD). WGDs provide a source of raw genetic material for evolutionary forces to act upon, resulting in the divergence of genes with altered or novel functions. The retention of multiple gene pairs (paralogs) in teleosts provides a unique opportunity to study how genes diversify and evolve after a WGD. This study examines the hypothesis that vitamin D receptor (VDR) paralogs (VDRα and VDRβ) from two distantly related teleost orders have undergone functional divergence subsequent to the teleost-specific WGD. VDRα and VDRβ paralogs were cloned from the Japanese medaka (Beloniformes) and the zebrafish (Cypriniformes). Initial transactivation studies using 1α, 25-dihydroxyvitamin D3 revealed that although VDRα and VDRβ maintain similar ligand potency, the maximum efficacy of VDRβ was significantly attenuated compared with VDRα in both species. Subsequent analyses revealed that VDRα and VDRβ maintain highly similar ligand affinities; however, VDRα demonstrated preferential DNA binding compared with VDRβ. Protein-protein interactions between the VDR paralogs and essential nuclear receptor coactivators were investigated using transactivation and mammalian two-hybrid assays. Our results imply that functional differences between VDRα and VDRβ occurred early in teleost evolution because they are conserved between distantly related species. Our results further suggest that the observed differences may be associated with differential protein-protein interactions between the VDR paralogs and coactivators. We speculate that the observed functional differences are due to subtle ligand-induced conformational differences between the two paralogs, leading to divergent downstream functions.

scholarly journals Stat1-Vitamin D Receptor Interactions Antagonize 1,25-Dihydroxyvitamin D Transcriptional Activity and Enhance Stat1-Mediated Transcription

2002 ◽  
Vol 22 (8) ◽  
pp. 2777-2787 ◽  
Author(s):  
Marcos Vidal ◽  
Chilakamarti V. Ramana ◽  
Adriana S. Dusso
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Cross Talk ◽  
Protein Interactions ◽  
Nuclear Accumulation ◽  
Protein Protein Interactions ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D ◽  
Key Enzyme ◽  
Ifn Γ

ABSTRACT The cytokine gamma interferon (IFN-γ) and the calcitropic steroid hormone 1,25-dihydroxyvitamin D (1,25D) are activators of macrophage immune function. In sarcoidosis, tuberculosis, and several granulomatoses, IFN-γ induces 1,25D synthesis by macrophages and inhibits 1,25D induction of 24-hydroxylase, a key enzyme in 1,25D inactivation, causing high levels of 1,25D in serum and hypercalcemia. This study delineates IFN-γ-1,25D cross talk in human monocytes-macrophages. Nuclear accumulation of Stat1 and vitamin D receptor (VDR) by IFN-γ and 1,25D promotes protein-protein interactions between Stat1 and the DNA binding domain of the VDR. This prevents VDR-retinoid X receptor (RXR) binding to the vitamin D-responsive element, thus diverting the VDR from its normal genomic target on the 24-hydroxylase promoter and antagonizing 1,25D-VDR transactivation of this gene. In contrast, 1,25D enhances IFN-γ action. Stat1-VDR interactions, by preventing Stat1 deactivation by tyrosine dephosphorylation, cooperate with IFN-γ/Stat1-induced transcription. This novel 1,25D-IFN-γ cross talk explains the pathogenesis of abnormal 1,25D homeostasis in granulomatous processes and provides new insights into 1,25D immunomodulatory properties.

scholarly journals Association of Vitamin D Receptor Gene Polymorphisms with Serum Vitamin D Levels in a Greek Rural Population (Velestino Study)

2021 ◽  
pp. 1-10
Author(s):  
Natalia Divanoglou ◽  
Despina Komninou ◽  
Eleni A. Stea ◽  
Anagnostis Argiriou ◽  
Grigorios Papatzikas ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Vitamin D Receptor ◽  
Rural Population ◽  
Gene Polymorphisms ◽  
Molecular Mechanisms ◽  
Vdr Gene ◽  
Increased Risk ◽  
Vitamin D Levels ◽  
Vdr Gene Polymorphisms

<b><i>Background/Aim:</i></b> An alarming increase in vitamin D deficiency even in sunny regions highlights the need for a better understanding of the genetic background of the vitamin D endocrine system and the molecular mechanisms of gene polymorphisms of the vitamin D receptor (VDR). In this study, the serum levels of 25(OH)D<sub>3</sub> were correlated with common VDR polymorphisms (<i>ApaI, BsmI, FokI</i>, and <i>TaqI</i>) in 98 subjects of a Greek homogeneous rural population. <b><i>Methods:</i></b> 25(OH)D<sub>3</sub> concentration was measured by ultra-HPLC, and the VDR gene polymorphisms were identified by quantitative real-time PCR followed by amplicon high-resolution melting analysis. <b><i>Results:</i></b> Subjects carrying either the B <i>BsmI</i> (OR: 0.52, 95% CI: 0.27–0.99) or t <i>TaqI</i> (OR: 2.06, 95%: 1.06–3.99) allele presented twice the risk for developing vitamin D deficiency compared to the reference allele. Moreover, subjects carrying 1, 2, or all 3 of these genotypes (BB/Bb, Tt/tt, and FF) demonstrated 2-fold (OR: 2.04, 95% CI: 0.42–9.92), 3.6-fold (OR: 3.62, 95% CI: 1.07–12.2), and 7-fold (OR: 6.92, 95% CI: 1.68–28.5) increased risk for low 25(OH)D<sub>3</sub> levels, respectively. <b><i>Conclusions:</i></b> Our findings reveal a cumulative effect of specific VDR gene polymorphisms that may regulate vitamin D concentrations explaining, in part, the paradox of vitamin D deficiency in sunny regions, with important implications for precision medicine.

Vitamin D Receptor Gene Polymorphisms and the Risk of Metabolic Syndrome (MetS): A Meta-Analysis

2020 ◽  
Vol 20 ◽  
Author(s):  
Hamidreza Totonchi ◽  
Ramazan Rezaei ◽  
Shokoofe Noori ◽  
Negar Azarpira ◽  
Pooneh Mokarram ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Vitamin D ◽  
Vitamin D Receptor ◽  
Protective Factor ◽  
Meta Analysis ◽  
Receptor Gene ◽  
Fixed Effect Model ◽  
Fixed Effect ◽  
Vdr Gene ◽  
Effect Model

Introduction: Several studies have assessed the association between the vitamin D receptor (VDR) polymorphism and risk of metabolic syndrome (MetS). However, the results were inconsistent and inconclusive. Therefore, we conducted a meta-analysis to clarify the exact association between the vitamin D receptor (VDR) polymorphisms and the risk of MetS. Methods: All accessible studies reporting the association between the FokI (rs2228570) or / and TaqI (rs731236) or/and BsmI (rs1544410) or/and ApaI (rs7975232 polymorphisms of the Vitamin D Receptor and susceptibility to MetS published prior to February 2019 were systematically searched in Web of Science, Scopus, and PubMed. After that, Odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were estimated to evaluate the strength of the association in five genetic models. Results: A total of 9 articles based on four gene variations, and comprising 3348 participants with 1779 metabolic syndrome patients were included. The overall results suggested a significant association between BsmI (rs1544410) polymorphism and MetS susceptibility in recessive model (OR, 0.72, 95% CI, 0.55-0.95, fixed effect model), allelic model (OR, 0.83, 95% CI, 0.72-0.95, fixed effect model), and bb vs BB (OR, 0.65, 95% CI, 0.46-0.93, fixed effect). However, no significant association was identified between TaqI (rs731236) polymorphism, ApaI (rs7975232) polymorphism, and FokI (rs2228570) polymorphism and MetS. Conclusion: This meta-analysis suggested an association between the BsmI (rs1544410) polymorphism and MetS. Indeed, BsmI (rs1544410) acts as a protective factor in the MetS. As a result, the VDR gene could be regarded as a promising pharmacological and physiological target in prevention or treatment of the MetS.

scholarly journals Study of vitamin D receptor gene polymorphisms in a cohort of myocardial infarction patients with coronary artery disease

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Damir Raljević ◽  
Viktor Peršić ◽  
Elitza Markova-Car ◽  
Leon Cindrić ◽  
Rajko Miškulin ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Vitamin D ◽  
Coronary Artery ◽  
Vitamin D Receptor ◽  
Gene Polymorphisms ◽  
Vdr Gene ◽  
Vdr Polymorphism ◽  
Vdr Gene Polymorphisms ◽  
Vdr Polymorphisms

Abstract Background Vitamin D deficiency is associated with cardiovascular diseases, including coronary artery diseases (CAD). As vitamin D manifests its biological function through its vitamin D receptor (VDR), VDR gene polymorphisms potentially affect VDR functionality and vitamin D activity. Therefore, the objective of this study was to analyze three well-studied VDR gene polymorphisms—Fok1 (rs2228570), BsmI (rs1544410) and Taq1 (rs731236)—in a cohort of CAD patients after acute myocardial infarction. Methods In the presented cross-sectional study, 155 participants with CAD after acute myocardial infarction and 104 participants in a control group without CAD were enrolled. The participants in both groups were Caucasians of European origin. The genotyping of VDR polymorphisms rs2228570, rs1544410 and rs731236 was assessed by RT-PCR. Results The results show an association between the T/T genotype of the BsmI (rs1544410) and the G/G genotype of the Taq1 (rs731236) VDR polymorphism and CAD patients after acute myocardial infarction. There was no association between the Fok1 (rs2228570) VDR polymorphism and CAD patients after acute myocardial infarction. Conclusion The presented results suggest a potential association of the BsmI (rs1544410) and Taq1 (rs731236) VDR polymorphisms with CAD patients after myocardial infarction.

Past environmental sun exposure and risk of multiple sclerosis: a role for the Cdx-2 Vitamin D receptor variant in this interaction

2009 ◽  
Vol 15 (5) ◽  
pp. 563-570 ◽  
Author(s):  
JL Dickinson ◽  
DI Perera ◽  
AF van der Mei ◽  
A-L Ponsonby ◽  
AM Polanowski ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Vitamin D ◽  
Vitamin D Receptor ◽  
Significant Interaction ◽  
Important Determinant ◽  
Sun Exposure ◽  
Population Based ◽  
Vdr Gene ◽  
Increased Risk ◽  
Group 2

Multiple studies have provided evidence for an association between reduced sun exposure and increased risk of multiple sclerosis (MS), an association likely to be mediated, at least in part, by the vitamin D hormonal pathway. Herein, we examine whether the vitamin D receptor ( VDR), an integral component of this pathway, influences MS risk in a population-based sample where winter sun exposure in early childhood has been found to be an important determinant of MS risk. Three polymorphisms within the VDR gene were genotyped in 136 MS cases and 235 controls, and associations with MS and past sun exposure were examined by logistic regression. No significant univariate associations between the polymorphisms, rs11574010 ( Cdx-2A > G), rs10735810 ( Fok1T >  C), or rs731236 ( Taq1C > T) and MS risk were observed. However, a significant interaction was observed between winter sun exposure during childhood, genotype at rs11574010, and MS risk ( P = 0.012), with the ‘G’ allele conferring an increased risk of MS in the low sun exposure group (≤2 h/day). No significant interactions were observed for either rs10735810 or rs731236, after stratification by sun exposure. These data provide support for the involvement of the VDR gene in determining MS risk, an interaction likely to be dependent on past sun exposure.

Structure, Function, Involvement in Diseases and Targeting of 14-3-3 Proteins: An Update

2018 ◽  
Vol 25 (1) ◽  
pp. 5-21 ◽  
Author(s):  
Ylenia Cau ◽  
Daniela Valensin ◽  
Mattia Mori ◽  
Sara Draghi ◽  
Maurizio Botta
Keyword(s):  
Protein Interactions ◽  
Molecular Mechanisms ◽  
Physiological Role ◽  
Specific Protein ◽  
Protein Protein Interactions ◽  
Cellular Processes ◽  
Protein Partners ◽  
High Sequence Homology ◽  
Small Molecule Modulators

14-3-3 is a class of proteins able to interact with a multitude of targets by establishing protein-protein interactions (PPIs). They are usually found in all eukaryotes with a conserved secondary structure and high sequence homology among species. 14-3-3 proteins are involved in many physiological and pathological cellular processes either by triggering or interfering with the activity of specific protein partners. In the last years, the scientific community has collected many evidences on the role played by seven human 14-3-3 isoforms in cancer or neurodegenerative diseases. Indeed, these proteins regulate the molecular mechanisms associated to these diseases by interacting with (i) oncogenic and (ii) pro-apoptotic proteins and (iii) with proteins involved in Parkinson and Alzheimer diseases. The discovery of small molecule modulators of 14-3-3 PPIs could facilitate complete understanding of the physiological role of these proteins, and might offer valuable therapeutic approaches for these critical pathological states.

Sign in / Sign up

Export Citation Format

Share Document