NDLI: Vitamin D-influenced gene expression via a ligand-independent, receptor-DNA complex intermediate.

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Vitamin D-influenced gene expression via a ligand-independent, receptor-DNA complex intermediate.

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Vitamin D-influenced gene expression via a ligand-independent, receptor-DNA complex intermediate.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Ross, T. K. Darwish, H. M. Deluca, H. F. Moss, V. E.
Description	Author Affiliation: Ross TK ( Department of Biochemistry, College of Agricultural and Life Sciences, University of Wisconsin-Madison 53706.);
Abstract	A lingering question regarding the regulation of target gene expression by 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] has been the delineation of vitamin D receptor (VDR)-DNA binding and transactivation. This report confirms that initial VDR-DNA interaction occurs in a ligand-independent fashion. An electrophoretic mobility-shift analysis demonstrated that VDR, derived from extracts of the small intestines of vitamin D-deficient rats, is capable of binding a vitamin D response element (DRE). Additional mobility-shift studies using either porcine-derived VDR or recombinant rat VDR from insect cells revealed DRE-binding capability in the absence of 1,25-(OH)2D3. The reactions were performed in various salt environments, with the maximum of porcine VDR-DRE and rat VDR-DRE binding detected at 100 mM and 150 mM KCl, respectively. The addition of 1,25-(OH)2D3 to an identical set of reaction mixtures resulted in increased DRE binding with greater affinities exhibited by both VDR types. These two phenomena were confirmed upon examination of an elution profile of VDR bound to DRE-linked Sepharose. When a linear KCl gradient was used for elution without the addition of 1,25-(OH)2D3, the peak of VDR was 205 mM KCl; the presence of exogenous hormone shifted the maximum VDR elution to a position corresponding to 265 mM KCl. Based on these data and previous reports on VDR-mediated transactivation, we propose a model for 1,25-(OH)2D3-influenced target gene expression.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	20
Volume Number	90
Language	English
Publisher	National Academy of Sciences
Publisher Date	1993-11-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Gene Expression Drug Effects Receptors, Calcitriol Physiology Vitamin D Pharmacology Animals DNA-Binding Proteins Metabolism Genes Macromolecular Substances Nuclear Proteins Osteocalcin Genetics Protein Binding Transcriptional Activation Vitamin D Deficiency Physiopathology Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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