Nucleic Acids Research, 1994, Vol. 22, No. 15 2902-2907
© 1994
MOLECULAR BIOLOGY |
Difference and similarity of DNA sequence recognized by VDR homodimer and VDR/RXR heterodimer
Department of Environmental Biochemistry, Faculty of Pharmaceutical Sciences, Osaka University 1-6 Yamada-oka, Suita, Osaka 565, Japan
*To whom correspondence should be addressed
Received June 3, 1994. Revised July 11, 1994. Accepted July 11, 1994.
Nuclear receptors for the thyroid hormone and vitamin A and D cooperate with the retinoid X receptor (RXR) in activating the transcription. Although the hormone response elements for these receptors have been proposed in which spacing of the direct repeated motifs determine the specificity (so called 3 – 4 – 5 rule), vitamin D response elements (VDREs) in the natural context consist of often imperfect direct repeats. Vitamin D receptor (VDR) alone can bind to the mouse osteopontin (mSPP–1) VDRE, which contains a direct repeat separated by 3 nucleotides, but not to the rat osteocalcin (rOST) VDRE having inexact direct repeat. The presence of RXR not only allows the VDR to bind to the rOST VDRE, but also increases the binding affinity for the mSPP–1 VDRE. The RXR/VDR heterodimer exhibits the similar affinity constants for the mSPP–1 VDRE and the rOST VDRE, in spite of the apparently different affinities for two VDREs of the VDR homodimer. A random oligonucleotide selection procedure revealed that the consensus sequence selected by the RXR homodimer is the direct repeat spaced by one A residue. In contrast, the sequences preferentially selected by the VDR homodimer and the VDR/RXR heterodimer are similar, which are the direct repeats spaced by 3 nucleotides. The difference and similarity of DNA sequence recognition are discussed.
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