vitamin d response element


Summary: A DNA sequence that is found in the promoter region of vitamin D regulated genes. Vitamin D receptor (RECEPTOR, CALCITRIOL) binds to and regulates the activity of genes containing this element.

Top Publications

  1. Carlberg C. Molecular basis of the selective activity of vitamin D analogues. J Cell Biochem. 2003;88:274-81 pubmed
    ..This provides them with some selectivity for DNA-dependent and -independent signaling pathways and VDRE structures. ..
  2. Seuter S, Väisänen S, Radmark O, Carlberg C, Steinhilber D. Functional characterization of vitamin D responding regions in the human 5-Lipoxygenase gene. Biochim Biophys Acta. 2007;1771:864-72 pubmed
    ..Since no functional vitamin D response element (VDRE) has been reported for this gene so far, we performed in silico screening of the whole 5-LO gene ..
  3. Matilainen M, Malinen M, Saavalainen K, Carlberg C. Regulation of multiple insulin-like growth factor binding protein genes by 1alpha,25-dihydroxyvitamin D3. Nucleic Acids Res. 2005;33:5521-32 pubmed
    ..In conclusion, IGFBP1, 3 and 5 are primary 1alpha,25(OH)2D3 target genes that in intact cells are each under the control of multiple VDREs. ..
  4. Kitazawa S, Kajimoto K, Kondo T, Kitazawa R. Vitamin D3 supports osteoclastogenesis via functional vitamin D response element of human RANKL gene promoter. J Cell Biochem. 2003;89:771-7 pubmed
    ..The results provide direct evidence that 1alpha,25(OH)(2)D(3) augments osteoclastogenesis by transactivating the human RANKL gene in osteoblastic cells through VDRE. ..
  5. Tavera Mendoza L, Wang T, Lallemant B, Zhang R, Nagai Y, Bourdeau V, et al. Convergence of vitamin D and retinoic acid signalling at a common hormone response element. EMBO Rep. 2006;7:180-5 pubmed
    ..These results show a limited crosstalk between 1,25D3 and RA signalling by means of overlapping nuclear receptor DNA binding specificities, and uncover a role for p19INK4D in control of cell survival. ..
  6. Turunen M, Dunlop T, Carlberg C, Väisänen S. Selective use of multiple vitamin D response elements underlies the 1 alpha,25-dihydroxyvitamin D3-mediated negative regulation of the human CYP27B1 gene. Nucleic Acids Res. 2007;35:2734-47 pubmed
    ..The down-regulation of the CYP27B1 gene has been proposed to involve a negative vitamin D response element (nVDRE) that is located approximately 500 bp upstream from transcription start site (TSS)...
  7. Hakim I, Bar Shavit Z. Modulation of TNF-alpha expression in bone marrow macrophages: involvement of vitamin D response element. J Cell Biochem. 2003;88:986-98 pubmed
    ..The receptor complex interacting with tnfVDRE found in the promoter of the cytokine gene is probably composed of VDR-RXR heterodimer. ..
  8. Wang T, Tavera Mendoza L, Laperriere D, Libby E, MacLeod N, Nagai Y, et al. Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005;19:2685-95 pubmed
    ..The combined approaches used here thus provide numerous insights into the direct target genes underlying the broad physiological actions of 1,25(OH)2D3. ..
  9. Wang X, Wang T, White J, Studzinski G. Induction of kinase suppressor of RAS-1(KSR-1) gene by 1, alpha25-dihydroxyvitamin D3 in human leukemia HL60 cells through a vitamin D response element in the 5'-flanking region. Oncogene. 2006;25:7078-85 pubmed
    ..Our findings offer a potential mechanism for a signaling pathway that contributes to 1,25D-induced monocytic differentiation of human myeloid leukemia cells. ..

More Information


  1. Pike J, Zella L, Meyer M, Fretz J, Kim S. Molecular actions of 1,25-dihydroxyvitamin D3 on genes involved in calcium homeostasis. J Bone Miner Res. 2007;22 Suppl 2:V16-9 pubmed publisher
    ..Our studies identified key regulatory regions within the TRPV6 and RANKL genes that are essential for their individual expression in the intestine and bone, respectively. ..
  2. Peng L, Malloy P, Feldman D. Identification of a functional vitamin D response element in the human insulin-like growth factor binding protein-3 promoter. Mol Endocrinol. 2004;18:1109-19 pubmed
    ..mechanism involved in 1,25-(OH)2D3 regulation of IGFBP-3 expression and to identify the putative vitamin D response element (VDRE) in the IGFBP-3 promoter...
  3. Roff A, Wilson R. A novel SNP in a vitamin D response element of the CYP24A1 promoter reduces protein binding, transactivation, and gene expression. J Steroid Biochem Mol Biol. 2008;112:47-54 pubmed publisher
    ..novel SNPs in the human CYP24A1 promoter, including one at nucleotide -279 occurring within the distal vitamin D response element (VDRE2)...
  4. Wang T, Nestel F, Bourdeau V, Nagai Y, Wang Q, Liao J, et al. Cutting edge: 1,25-dihydroxyvitamin D3 is a direct inducer of antimicrobial peptide gene expression. J Immunol. 2004;173:2909-12 pubmed
    ..1,25(OH)(2)D(3) thus directly regulates antimicrobial peptide gene expression, revealing the potential of its analogues in treatment of opportunistic infections. ..
  5. Gutierrez S, Liu J, Javed A, Montecino M, Stein G, Lian J, et al. The vitamin D response element in the distal osteocalcin promoter contributes to chromatin organization of the proximal regulatory domain. J Biol Chem. 2004;279:43581-8 pubmed
    ..of the transcriptionally active OC promoter are not enhanced in the absence of a functional vitamin D response element (VDRE)...
  6. Kim S, Yamazaki M, Zella L, Shevde N, Pike J. Activation of receptor activator of NF-kappaB ligand gene expression by 1,25-dihydroxyvitamin D3 is mediated through multiple long-range enhancers. Mol Cell Biol. 2006;26:6469-86 pubmed
    ..We mapped these activities to an unusual but functionally active vitamin D response element and to several potential GC response elements located over a more extensive region within the RL-DCR...
  7. Deb D, Wang Y, Zhang Z, Nie H, Huang X, Yuan Z, et al. Molecular mechanism underlying 1,25-dihydroxyvitamin D regulation of nephrin gene expression. J Biol Chem. 2011;286:32011-7 pubmed publisher
    ..Nephrin up-regulation likely accounts for part of the renoprotective activity of vitamin D. ..
  8. Chen H, Reed G, Guardia J, Lakhan S, Couture O, Hays E, et al. Vitamin D directly regulates Mdm2 gene expression in osteoblasts. Biochem Biophys Res Commun. 2013;430:370-4 pubmed publisher
    ..Our results indicate that 1,25-dihydroxy vitamin D3 and its receptor have a role in the regulation of P2-initiated Mdm2 gene expression in a p53-dependent way. ..
  9. Okazaki T, Nishimori S, Ogata E, Fujita T. Vitamin D-dependent recruitment of DNA-PK to the chromatinized negative vitamin D response element in the PTHrP gene is required for gene repression by vitamin D. Biochem Biophys Res Commun. 2003;304:632-7 pubmed
    ..Furthermore, DNA-PKcs could phosphorylate VDR in vitro. We raise a possibility that a conformational change of VDR through its phosphorylation mediated by DNA-PKcs underlies the mechanism of gene repression by 1,25 vitamin D3-bound VDR. ..
  10. Tashiro K, Ishii C, Ryoji M. Role of distal upstream sequence in vitamin D-induced expression of human CYP24 gene. Biochem Biophys Res Commun. 2007;358:259-65 pubmed
    ..Further upstream sequence and the 5'-untranslated region did not appear to play a major role in the vitamin D response. ..
  11. Kato S, Kim M, Yamaoka K, Fujiki R. Mechanisms of transcriptional repression by 1,25(OH)2 vitamin D. Curr Opin Nephrol Hypertens. 2007;16:297-304 pubmed
    ..Given this, the mechanisms behind vitamin D-induced transcriptional repression are probably more complex than those of vitamin D-induced transactivation. ..
  12. Kitareewan S, Blumen S, Sekula D, Bissonnette R, Lamph W, Cui Q, et al. G0S2 is an all-trans-retinoic acid target gene. Int J Oncol. 2008;33:397-404 pubmed
    ..Taken together, these findings indicate G0S2 is an RA target gene. The functional role of G0S2 in retinoid response of APL warrants further study. ..
  13. Barnett C, Krebs J. WSTF does it all: a multifunctional protein in transcription, repair, and replication. Biochem Cell Biol. 2011;89:12-23 pubmed publisher
    ..This review will describe the three known WSTF-containing complexes and discuss their various roles as well as mechanisms of regulating WSTF activity. ..
  14. Gombart A, Saito T, Koeffler H. Exaptation of an ancient Alu short interspersed element provides a highly conserved vitamin D-mediated innate immune response in humans and primates. BMC Genomics. 2009;10:321 pubmed publisher
    ..Evolutionary selection to place the primate CAMP gene under regulation of the vitamin D pathway potentiates the innate immune response and may counter the anti-inflammatory properties of vitamin D. ..
  15. Xie W, He Y, Huo D, Huang Y, Wu W. A mimic of phosphorylated prolactin inhibits human breast cancer cell proliferation via upregulation of p21 waf1. Med Oncol. 2010;27:1340-5 pubmed publisher
    ..One (p21 VDRE Luc) has the vitamin D response element (VDRE) in the p21 promoter region; the other (p21 NO-VDRE Luc) does not...
  16. Stambolsky P, Tabach Y, Fontemaggi G, Weisz L, Maor Aloni R, Siegfried Z, et al. Modulation of the vitamin D3 response by cancer-associated mutant p53. Cancer Cell. 2010;17:273-85 pubmed publisher
    ..Furthermore, mutp53 increases the nuclear accumulation of VDR. Importantly, mutp53 converts vitamin D into an antiapoptotic agent. Thus, p53 status can determine the biological impact of vitamin D on tumor cells. ..
  17. Lisse T, Hewison M, Adams J. Hormone response element binding proteins: novel regulators of vitamin D and estrogen signaling. Steroids. 2011;76:331-9 pubmed publisher
    ..In addition the review also describes other molecules that are known to influence nuclear receptor signaling through interaction with hormone response elements. ..
  18. Ji L, Gupta M, Feldman B. Vitamin D Regulates Fatty Acid Composition in Subcutaneous Adipose Tissue Through Elovl3. Endocrinology. 2016;157:91-7 pubmed publisher
    ..These data suggest that vitamin D/VDR tissue specifically modulates FA composition in sc WAT through direct regulation of Elovl3 expression. ..
  19. Shen Z, Zhang X, Tang J, Kasiappan R, Jinwal U, Li P, et al. The coupling of epidermal growth factor receptor down regulation by 1alpha,25-dihydroxyvitamin D3 to the hormone-induced cell cycle arrest at the G1-S checkpoint in ovarian cancer cells. Mol Cell Endocrinol. 2011;338:58-67 pubmed publisher
    ..A novel vitamin D response element was identified in intron 1 of the EGFR genome, a known hotspot for its transcriptional regulation...
  20. Cui J, Ma C, Qiu J, Ma X, Wang X, Chen H, et al. A novel interaction between insulin-like growth factor binding protein-6 and the vitamin D receptor inhibits the role of vitamin D3 in osteoblast differentiation. Mol Cell Endocrinol. 2011;338:84-92 pubmed publisher
    ..These results demonstrate that IGFBP-6 inhibits osteoblastic differentiation mediated by 1,25(OH)(2)D(3) and the VDR through interacting with the VDR and inhibiting its function. This is a novel mechanism for IGFBP-6. ..
  21. Chun R, Peercy B, Adams J, Hewison M. Vitamin D binding protein and monocyte response to 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D: analysis by mathematical modeling. PLoS ONE. 2012;7:e30773 pubmed publisher
    ..These novel mathematical models underline the importance of DBP as a determinant of vitamin D 'status' in vivo, with future implications for clinical studies of vitamin D status and supplementation. ..
  22. Eloranta J, Hiller C, Jüttner M, Kullak Ublick G. The SLCO1A2 gene, encoding human organic anion-transporting polypeptide 1A2, is transactivated by the vitamin D receptor. Mol Pharmacol. 2012;82:37-46 pubmed publisher
    ..Our results suggest that pharmacological administration of vitamin D(3) may allow modulation of intestinal absorption of OATP1A2 transport substrates. ..
  23. Satoh J, Tabunoki H. Molecular network of chromatin immunoprecipitation followed by deep sequencing-based vitamin D receptor target genes. Mult Scler. 2013;19:1035-45 pubmed publisher
    ..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. ..
  24. Swami S, Krishnan A, Peng L, Lundqvist J, Feldman D. Transrepression of the estrogen receptor promoter by calcitriol in human breast cancer cells via two negative vitamin D response elements. Endocr Relat Cancer. 2013;20:565-77 pubmed publisher
    ..The suppression of ER expression and estrogen-mediated signaling by calcitriol in BCa cells suggests that vitamin D may be useful in the treatment of ER+ BCa. ..
  25. Malloy P, Feldman B. Cell-autonomous regulation of brown fat identity gene UCP1 by unliganded vitamin D receptor. Mol Endocrinol. 2013;27:1632-42 pubmed publisher
    ..Importantly, we found that this process occurs cell autonomously and is independent of the physiologic VDR hormone ligand, 1,25-dihydroxyvitamin D. These results identify a mechanism for modulating energy balance in humans. ..
  26. van den Bemd G, Jhamai M, Staal A, Van Wijnen A, Lian J, Stein G, et al. A central dinucleotide within vitamin D response elements modulates DNA binding and transactivation by the vitamin D receptor in cellular response to natural and synthetic ligands. J Biol Chem. 2002;277:14539-46 pubmed
  27. Byford V, Strugnell S, Coldwell R, Schroeder N, Makin H, Knutson J, et al. Use of vitamin D(4) analogs to investigate differences in hepatic and target cell metabolism of vitamins D(2) and D(3). Biochim Biophys Acta. 2002;1583:151-66 pubmed
    ..We conclude that vitamin D(4) analogs and their metabolites offer valuable insights into vitamin D analog design, metabolic enzymes and maybe useful clinically. ..
  28. Johnson C, Hershberger P, Trump D. Vitamin D-related therapies in prostate cancer. Cancer Metastasis Rev. 2002;21:147-58 pubmed
    ..Studies continue to define the MTD of calcitriol whichcan be safely administered on this intermittent schedule either alone or with other agents and to evaluate the mechanisms of calcitriol effects in prostate cancer. ..
  29. Tovar Sepulveda V, Falzon M. Prostate cancer cell type-specific regulation of the human PTHrP gene via a negative VDRE. Mol Cell Endocrinol. 2003;204:51-64 pubmed
    ..The human PTHrP gene contains a sequence element homologous to the negative vitamin D response element within the parathyroid hormone gene...
  30. Hsieh J, Whitfield G, Jurutka P, Haussler C, Thatcher M, Thompson P, et al. Two basic amino acids C-terminal of the proximal box specify functional binding of the vitamin D receptor to its rat osteocalcin deoxyribonucleic acid-responsive element. Endocrinology. 2003;144:5065-80 pubmed
    ..Examination of DNA specificity element amino acids in other nuclear receptors in terms of conservation and base contact in cocrystal structures supports the conclusion that these residues are crucial for selective DNA recognition. ..
  31. Weyts F, Dhawan P, Zhang X, Bishop J, Uskokovic M, Ji Y, et al. Novel Gemini analogs of 1alpha,25-dihydroxyvitamin D(3) with enhanced transcriptional activity. Biochem Pharmacol. 2004;67:1327-36 pubmed
    ..and THP-1 differentiation and 5-50-fold more potent in inducing transcription from the osteocalcin vitamin D response element or the 25-hydroxyvitamin D(3)-24-hydroxylase (24OHase) promoter. In vivo, following i.p...
  32. Lu X, Farmer P, Rubin J, Nanes M. Integration of the NfkappaB p65 subunit into the vitamin D receptor transcriptional complex: identification of p65 domains that inhibit 1,25-dihydroxyvitamin D3-stimulated transcription. J Cell Biochem. 2004;92:833-48 pubmed
    ..These treatments caused stable incorporation of p65 into the transcription complex bound to the vitamin D response element (VDRE) of the osteocalcin promoter...
  33. Ellfolk M, Norlin M, Wikvall K. Isolation and properties of the CYP2D25 promoter: transcriptional regulation by vitamin D3 metabolites. Biochem Biophys Res Commun. 2006;345:568-72 pubmed
    ..The CYP2D25 promoter contains a putative vitamin D response element (VDRE)...
  34. Pascussi J, Robert A, Nguyen M, Walrant Debray O, Garabedian M, Martin P, et al. Possible involvement of pregnane X receptor-enhanced CYP24 expression in drug-induced osteomalacia. J Clin Invest. 2005;115:177-86 pubmed
    ..These data suggest that xenobiotics and drugs can modulate CYP24 gene expression and alter vitamin D(3) hormonal activity and calcium homeostasis through the activation of PXR...
  35. Jaaskelainen T, Huhtakangas J, Mäenpää P. Negative regulation of human parathyroid hormone gene promoter by vitamin D3 through nuclear factor Y. Biochem Biophys Res Commun. 2005;328:831-7 pubmed
    ..8 cells. These results indicate that 1,25(OH)2D3 may affect transcription of the human PTH gene both by competitive binding of VDR and NF-Y, and by modulating transcriptional activity of NF-Y. ..
  36. Wehmeier K, Mazza A, Hachem S, Ligaray K, Mooradian A, Wong N, et al. Differential regulation of apolipoprotein A-I gene expression by vitamin D receptor modulators. Biochim Biophys Acta. 2008;1780:264-73 pubmed
    ..Gel shift assays showed that none of the treatments resulted in a change in site A binding activity. These results indicate that VDR modulators in hepatocytes and intestinal cells differentially regulate expression of the apo A-I gene. ..
  37. Kumar R, Iachini D, Neilsen P, Kaplan J, Michalakas J, Anderson P, et al. Systematic characterisation of the rat and human CYP24A1 promoter. Mol Cell Endocrinol. 2010;325:46-53 pubmed publisher
    ..form of vitamin D, 1,25-dihydroxyvitamin D (1,25D) ligands VDR (vitamin D receptor) and binds to the vitamin D response element (VDRE) located within target genes to regulate their transcription...
  38. Ohno A, Shimizu M, Yamada S. Fluorinated vitamin D analogs to probe the conformation of vitamin D in its receptor complex: 19F-NMR studies and biological activity. Chem Pharm Bull (Tokyo). 2002;50:475-83 pubmed
    ..This biological information in combination with the NMR properties indicates that 2a and 4a are promising probes for studying the VDR-bound A-ring conformation of vitamin D. ..
  39. Ito M, Sakai Y, Furumoto M, Segawa H, Haito S, Yamanaka S, et al. Vitamin D and phosphate regulate fibroblast growth factor-23 in K-562 cells. Am J Physiol Endocrinol Metab. 2005;288:E1101-9 pubmed
    ..sites, including MZF1, GATA-1 and c-Ets-1 motifs, but it did not contain the typical sequences of the vitamin D response element. Plasmids encoding 554-bp (pGL/-0.6), 364-bp (pGL/-0.4) and 200-bp (pGL/-0...
  40. Ito Y, Inoue D. [Gene, structure and biosynthesis of parathyroid hormone]. Nihon Rinsho. 2005;63 Suppl 10:274-7 pubmed
  41. Bobilev I, Novik V, Levi I, Shpilberg O, Levy J, Sharoni Y, et al. The Nrf2 transcription factor is a positive regulator of myeloid differentiation of acute myeloid leukemia cells. Cancer Biol Ther. 2011;11:317-29 pubmed
    ..Our findings suggest that the Nrf2/ARE pathway plays an important part in the cooperative induction of myeloid leukemia cell differentiation by 1,25D and a plant polyphenol. ..
  42. Okazaki T. [Parathyroid hormone--its localization and transcriptional regulation]. Nihon Rinsho. 2005;63 Suppl 10:284-91 pubmed
  43. Chen X, Chen F, Liu S, Glaeser H, Dawson P, Hofmann A, et al. Transactivation of rat apical sodium-dependent bile acid transporter and increased bile acid transport by 1alpha,25-dihydroxyvitamin D3 via the vitamin D receptor. Mol Pharmacol. 2006;69:1913-23 pubmed
    ..The activation by 1,25(OH)(2)D(3) was abrogated after site-directed mutagenesis or deletion of the vitamin D response element (VDRE) in the ASBT promoter...
  44. Ramirez A, Wongtrakool C, Welch T, Steinmeyer A, Zugel U, Roman J. Vitamin D inhibition of pro-fibrotic effects of transforming growth factor beta1 in lung fibroblasts and epithelial cells. J Steroid Biochem Mol Biol. 2010;118:142-50 pubmed publisher
    ..Fibroblasts transfected with a vitamin D response element-reporter construct and exposed to the active vitamin D metabolite, 1,25(OH)(2)D(3), showed increased ..
  45. Ramagopalan S, Maugeri N, Handunnetthi L, Lincoln M, Orton S, Dyment D, et al. Expression of the multiple sclerosis-associated MHC class II Allele HLA-DRB1*1501 is regulated by vitamin D. PLoS Genet. 2009;5:e1000369 pubmed publisher
    ..Sequence analysis localised a single MHC vitamin D response element (VDRE) to the promoter region of HLA-DRB1...
  46. Xu H, McCann M, Zhang Z, Posner G, Bingham V, El Tanani M, et al. Vitamin D receptor modulates the neoplastic phenotype through antagonistic growth regulatory signals. Mol Carcinog. 2009;48:758-72 pubmed publisher
    ..These findings may be relevant to the cell- or tissue-specificity of vitamin D growth regulation. ..
  47. Taber L, Adams L, Teegarden D. Mechanisms of nuclear vitamin D receptor resistance in Harvey-ras-transfected cells. J Nutr Biochem. 2009;20:629-37 pubmed publisher
  48. Carlberg C, Dunlop T. The impact of chromatin organization of vitamin D target genes. Anticancer Res. 2006;26:2637-45 pubmed
    ..These results will have an impact on the development of therapeutic regimes for diseases, such as cancer, that use 1alpha,25(OH)2D3 and its analogs. ..
  49. Castillo A, Sánchez Martínez R, Jiménez Lara A, Steinmeyer A, Zugel U, Aranda A. Characterization of vitamin D receptor ligands with cell-specific and dissociated activity. Mol Endocrinol. 2006;20:3093-104 pubmed
    ..recruit p160 and VDR-interacting protein 205 coactivators, is as potent as 1,25-(OH)(2)D(3) to stimulate vitamin D response element-dependent transcription in HeLa cells, and acts as a superagonist in human embryonic kidney 293T cells...
  50. Saeki M, Kurose K, Tohkin M, Hasegawa R. Identification of the functional vitamin D response elements in the human MDR1 gene. Biochem Pharmacol. 2008;76:531-42 pubmed publisher
  51. Ormerod A, Xing Z, Pedigo N, Mishra A, Kaetzel D. The calcitriol analogue EB1089 impairs alveolarization and induces localized regions of increased fibroblast density in neonatal rat lung. Exp Lung Res. 2008;34:155-82 pubmed publisher
    ..effective than 1,25-(OH)2D3(EB1089 > CB1093 > MC1288 > 1,25-(OH)2D3) in the activation of a vitamin D response element from the platelet-derived growth factor (PDGF)-A gene, whose expression is essential for normal ..
  52. Kobayashi E, Shimazaki M, Miyamoto Y, Masuno H, Yamamoto K, DeLuca H, et al. Structure-activity relationships of 19-norvitamin D analogs having a fluoroethylidene group at the C-2 position. Bioorg Med Chem. 2007;15:1475-82 pubmed
    ..On the basis of the biological activities and a docking simulation based on X-ray crystallographic analysis of the VDR ligand-binding pocket, the structure-activity relationships of the fluorinated 19-norvitamin D analogs are discussed. ..