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DNA bending is induced by binding of vitamin D receptor‐retinoid X receptor heterodimers to vitamin D response elements
Author(s) -
KimmelJehan Christine,
Darwish Hisham M.,
Strugnell Steve A.,
Jehan Frédéric,
Wiefling Bridgette,
DeLuca Hector F.
Publication year - 1999
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/(sici)1097-4644(19990801)74:2<220::aid-jcb8>3.0.co;2-t
Subject(s) - calcitriol receptor , retinoid x receptor , endocrinology , medicine , thyroid hormone receptor , hormone response element , biology , chemistry , biophysics , microbiology and biotechnology , nuclear receptor , vitamin d and neurology , hormone , biochemistry , transcription factor , gene , estrogen receptor , cancer , breast cancer
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 RXRβ 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. J. Cell. Biochem. 74:220–228, 1999. © 1999 Wiley‐Liss, Inc.