Vitamin D Receptor Promoter and Regulation of Receptor Expression

Esteban, Luis; Eisman, John A.; Gardiner, Edith M.

doi:10.1016/b978-012252687-9/50015-2

Cited by 10 publications

(12 citation statements)

References 190 publications

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“…Thus, the receptor’s expression in cells is a requirement for response, and the receptor’s concentration itself a key component of sensitivity to the hormone as well. While little is known of the molecular determinants of basal expression of the VDR in cells, the VDR gene is known to be regulated by a variety of hormones including PTH, retinoic acid, and the glucocorticoids (56). Perhaps most interesting is the ability of 1,25(OH) 2 D 3 to increase the level of VDR gene expression itself.…”

Section: New Approaches Reveal New Insights Into Vitamin D3-mediated mentioning

confidence: 99%

The Vitamin D Receptor: New Paradigms for the Regulation of Gene Expression by 1,25-Dihydroxyvitamin D3

Pike

Meyer

2010

Endocrinology and Metabolism Clinics of North America

330

173

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SYNOPSISThe actions of the vitamin D hormone 1,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ) are mediated by the vitamin D receptor (VDR), a ligand-activated transcription factor that functions to control gene expression. Following ligand activation, the VDR binds directly to specific sequences located near promoters and recruits a variety of coregulatory complexes that perform the additional functions required to modify transcriptional output. Recent advances in transcriptional regulation, which permit the unbiased identification of the regulatory regions of genes, are providing new insight into how genes are regulated. Surprisingly, gene regulation requires the orchestrated efforts of multiple modular enhancers often located many kilobases upstream, downstream or within the transcription units themselves. These studies are transforming our understanding of how 1,25(OH) 2 D 3 regulates gene transcription. KeywordsTranscription; ChIP-chip analysis; distal enhancers; RNA polymerase II; histone H4 acetylation; VDR gene INTRODUCTIONResearch during the past two decades has established that the diverse biological actions of 1,25-dihydroyxyvitamin D 3 (1,25(OH) 2 D 3 ) are initiated through precise changes in gene expression which are mediated by an intracellular vitamin D receptor (VDR) (1). Activation of the VDR through direct interaction with 1,25(OH) 2 D 3 prompts the receptor's rapid binding to regulatory regions of target genes, where it acts to nucleate the formation of large protein complexes whose functional activities are essential for directed changes in transcription (2). In most target cells, these actions trigger the expression of networks of target genes whose functional activities combine to orchestrate specific biological responses. These responses are tissue-specific and range from highly complex actions essential for homeostatic control of mineral metabolism to focal actions that control the growth, differentiation and functional activity of numerous cell types including those of the immune system, skin, the pancreas and bone as well as many other targets that are described in this issue devoted to vitamin D (3). In these tissues, gene targets are numerous. New studies combined with new techniques are now revealing a surprising increase in mechanistic complexity wherein multiple regulatory regions, * To whom correspondence should be addressed: Dr. J. W. Pike, Department of Biochemistry, University of 433 Babcock Drive, Madison, WI 53706. Tel: (608) 262-8229; fax: (608) 263-7609; pike@biochem.wisc.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Pub...

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Section: New Approaches Reveal New Insights Into Vitamin D3-mediated mentioning

confidence: 99%

The Vitamin D Receptor: New Paradigms for the Regulation of Gene Expression by 1,25-Dihydroxyvitamin D3

Pike

Meyer

2010

Endocrinology and Metabolism Clinics of North America

330

173

View full text Add to dashboard Cite

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“…1,25(OH) 2 D 3 is also able to regulate the expression of the VDR gene itself. VDR autoregulation has been observed in a variety of bonerelated culture models and in certain vitamin D 3 target tissues in vivo [3]. While there is sufficient evidence to support the * Corresponding author.…”

Section: Introductionmentioning

confidence: 97%

“…1,25-Dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ) regulates mineral homeostasis in vertebrates through its ability to control the expression of gene networks in the kidney, intestine, and bone. Its actions are mediated by the vitamin D receptor (VDR), which functions as an RXR heterodimer and aids in the recruitment of coregulatory proteins necessary for chromatin modification and transcriptional activation [1].…”

Section: Introductionmentioning

confidence: 99%

Enhancers located in the vitamin D receptor gene mediate transcriptional autoregulation by 1,25-dihydroxyvitamin D3

Zella

Kim

Shevde

et al. 2007

The Journal of Steroid Biochemistry and Molecular Biology

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“…VDR contains a VDRE sequence within its own promoter [47], and 1,25D3 is known to regulate expression of its own receptor [48]; therefore, we also measured VDR transcripts. For these experiments, SV40 cell lines were treated with 1,25D3 (10 −8 M) for 6 h or 24 h, and total RNA was subjected to qPCR using SYBR green.…”

Section: Resultsmentioning

confidence: 99%

The vitamin D3 transcriptomic response in skin cells derived from the Atlantic bottlenose dolphin

Ellis

Gattoni‐Celli

Mancia

et al. 2009

Developmental & Comparative Immunology

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The Atlantic bottlenose dolphin has attracted attention due to the evident impact that environmental stressors have taken on its health. In order to better understand the mechanisms linking environmental health with dolphin health, we have established cell cultures from dolphin skin as in vitro tools for molecular evaluations. The vitamin D3 pathway is one mechanism of interest because of its well established chemopreventative and immunomodulatory properties in terrestrial mammals. On the other hand, little is known of the physiological role of this molecule in aquatic animals. 1,25-dihydroxyvitamin D3 (1,25D3), the bioactive and hormonal form of vitamin D3, exerts its biological function by binding to the vitamin D receptor (VDR), a ligand-activated regulator of gene transcription. Therefore, we investigated the transcriptomic changes induced by 1,25D3 administration in dolphin skin cells. Identification of specific genes activated by 1,25D3 has provided clues to the physiological function of the vitamin D3 pathway in the dolphin. We found that exposure of the cells to 1,25D3 upregulated transactivation of a vitamin D-sensitive promoter. cDNA microarray analysis, using a novel dolphin array, identified specific gene targets within this pathway, and real-time PCR (qPCR) confirmed the enhanced expression of select genes of interest. These transcriptional changes correlated with an increase in VDR levels. This is the first report of the presence and activation of the vitamin D3 pathway in a marine mammal, and our experimental results demonstrate a number of similarities to terrestrial animals. Conservation of this pathway in the Atlantic bottlenose dolphin is consistent with the importance of nonclassic functions of vitamin D3, such as its role in innate immunity, similar to what has been demonstrated in other mammals.

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Vitamin D Receptor Promoter and Regulation of Receptor Expression

Cited by 10 publications

References 190 publications

The Vitamin D Receptor: New Paradigms for the Regulation of Gene Expression by 1,25-Dihydroxyvitamin D3

The Vitamin D Receptor: New Paradigms for the Regulation of Gene Expression by 1,25-Dihydroxyvitamin D3

Enhancers located in the vitamin D receptor gene mediate transcriptional autoregulation by 1,25-dihydroxyvitamin D3

The vitamin D3 transcriptomic response in skin cells derived from the Atlantic bottlenose dolphin

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