The vitamin D receptor (VDR) is a transcription factor believed to function as a heterodimer with the retinoid X receptor (RXR). However, it was reported that, on putative vitamin D response elements (VDREs) within the rat 9k and mouse 28k calcium binding protein genes (rCaBP 9k and mCaBP 28k), VDR
DNA bending is induced by binding of vitamin D receptor-retinoid X receptor heterodimers to vitamin D response elements
✍ Scribed by Christine Kimmel-Jehan; Hisham M. Darwish; Steve A. Strugnell; Frédéric Jehan; Bridgette Wiefling; Hector F. DeLuca
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 190 KB
- Volume
- 74
- Category
- Article
- ISSN
- 0730-2312
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✦ Synopsis
The ability of vitamin D receptor-retinoid X receptor (VDR-RXR) heterodimers to induce a DNA bend upon binding to various vitamin D response elements (VDRE) has been investigated by circular permutation and phasing analysis. Recombinant rat VDR expressed in the baculovirus system and purified recombinant human RXR have been used. The VDREs were from 1,25-dihydroxyvitamin D 3 (1,25-[OH] 2 D 3 ) enhanced genes (rat osteocalcin, rOC; mouse osteopontin, mOP, and rat 1,25-dihydroxyvitamin D 3 -24-hydroxylase, r24-OHase), and a 1,25-(OH) 2 D 3 repressed gene (human parathyroid hormone, hPTH). As shown by circular permutation analysis, VDR-RXR induced a distortion in DNA fragments containing various VDREs. Calculated distortion angles were similar in magnitude (57°, 56°, 61°, and 59°, respectively for rOC, mOP, r24-Ohase, and hPTH). The distortions took place with or without a 1,25-(OH) 2 D 3 ligand. The centers of the apparent bend were found in the vicinity of the midpoint of all VDREs, except for rOC VDRE which was found 4 bp upstream. Phasing analysis was performed with DNA fragments containing mOP VDRE and revealed that VDR-RXR heterodimers induced a directed bend of 26°, not influenced by the presence of hormone. In this study we report that similar to other members of the steroid and thyroid nuclear receptor superfamily, VDR-RXR heterodimers induce DNA bending.
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