Vitamin D responsive elements

Hormones and vitamins also play a role in regulation of ASBT. Both glucocorticoid receptor ligands and co-expression of the glucocorticoid receptor gene increased activity of ASBT, while there is also evidence that dihydroxy vitamin D binds directly to the vitamin D response element and increases expression of ASBT, leading to increased transport of bile acids into the enterocyte. ... 

GGGTGAnnnGGGTGA Vitamin D-responsive element direct repeats... 

Canaff, L and Hendy, GN, 2002, Human calcium-sensing receptor gene. Vitamin D response elements in promoters PI and P2 confer transcriptional responsiveness to 1,25-dihydroxyvitamin D, J Biol Chem 277 30337-30350... 

Thompson PD, Jurutka PW, Whitfield GK, et al. Liganded VDR induces CYP3A4 in small intestinal and colon cancer cells via DR3 and ER6 vitamin D responsive elements. Biochem Biophys Res Commun 2002 299(5) 730-738. 

Figure 30-4. Hormone action of 1,25-dihydroxyvitamin D. VDR, vitamin D receptor RXR, retinoic acid receptor VDRE, vitamin D response element.

Calcitriol acts like a steroid hormone, binding to, and activating, nuclear receptors that modulate gene expression. More than 50 genes are known to be regulated by calcitriol (see Table 3.3), but vitamin D response elements have only been identified in a relatively small number, including calcidiol 1-hydroxylase and 24-hydroxylase calbindin, a calcium binding protein in the... 

The vitamin D receptor acts mainly as a heterodimer with the retinoid X receptor (RXR Section 2.3.2.1). Binding of calcitriol induces a conformational change in the receptor protein, permitting dimerization with occupied or unoccupied RXR, followed by phosphorylation to activate binding to the vitamin D response element on DNA (DeLuca and Zierold, 1998). Abnormally high concentrations of 9-cis-retinoic acid result in sequestration of RXR as the homodimers, meaning that it is unavailable to form heterodimers with the vitamin D receptor (or other receptors) excessive vitamin A can therefore antagonize the nuclear actions of vitamin D (Haussler et al., 1995 Rohde et al., 1999). 

Darwish, H and Ukfl.tica, H. P, (1996), Analysis of binding of the 1,25-dlhydrox vitamln Dj receptor to positive and negative vitamin D response elements. Arrh. iiifKbi ni. Biophys. 334, 223-234. 

Mackey, S. L-, Heymont,). L-, Kionenberg, H. M., and Dcmay, M. B. (1996), Vitamin D receptor binding to the negative human parathyroid hormone vitamin D response element does not require the retinoid X receptor, Mof. Endocrine . ID, 298-305. 

Zou, A., Elgort, M. G., and Allegretto, E. A. (1997). Retinoid X receptor (RXR) ligands activate the human 25-hydroxyvitamin D3 24 hydroxylase promoter via RXR heterodimer binding to two vitamin D-responsive elements and elicit additive effects with 1,25-dihydroxyvitamin D3. /. Biol Chem. 272,19027-19034. 

As with vitamin A, mast of the effects of vitamin D involve a nuclear receptor. The vitamin D receptor is a member of the steroid/thyroid hormone superfamily of receptors. When I a,2S-OHD binds to its receptor, the complex forms a hetcrodimer with an unoccupied RXR. This heterodimer subsequently binds to the regulatory regions on specific genes in target tissue. These regions are called vitamin D response elements (VDREs). The binding to VDREs can increase or decrease expression of genes. The proteins thus made carry out the functions of vitamin D. 

Turunen, M.M. et al. (2007) Selective use of multiple vitamin D response elements underlies the la,25-dihydroxyvitamin D3-mediated negative regulation of the human CYP27B1 gene. Nucleic Acids Research, 35, 2734—2747. 

Kitazawa, S. et al. (2003) Vitamin D3 supports osteodastogenesis via functional vitamin D response element of human RANKL gene promoter. Journal of Cellular Biochemistry, 89, 771—111. 

Zierold, C., H.M. Darwish, and H.E DeLuca (1994). Identification of a vitamin D-response element in the rat calcidiol (25-hydroxyvitamin D3) 24-hydroxylase gene. Proc. Natl. Acad. Sci. USA 91, 900-902. 

Ohyama, Y., K. Ozono, M. Uchida, T. Shinki, S. Kato, T. Suda et al. (1994). Identification of a vitamin D-responsive element in the 5 -flanking region of the rat 25-hydroxyvitamin D3 24-hydroxylase gene. J. Biol. Chem. 269, 10545-10550. 

PXR (liganded) can activate the P450 24A1 gene by directly binding to and transactivating vitamin D-responsive elements within the promoter region [2459],... 

Identification of a vitamin D-responsive element in the 5 -flanking region of the rat 25-hydroxyvi-tamin D3 24-hydroxylase gene. J Biol Chem 269 10545-10550... 

Omdahl JL, May BK (1996) Transcriptional synergism between vitamin D-responsive elements in the rat 25-hydroxyvitamin Dj 24-hydroxylase (CYP24) promoter. J Biol Chem 271 29715-29721... 

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