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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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