Analysis of binding of the 1,25-dihydroxyvitamin D3 receptor to positive and negative vitamin D response elements.
The binding of the 1,25-dihydroxyvitamin D3 receptor to the vitamin D response elements (VDREs) in the rat osteocalcin (OSC-DRE), mouse osteopontin (MOP-DRE), rat calbindin D-9k (CaBP-DRE), and human parathyroid hormone genes (PTH-DRE) was studied. Binding of VDR to the three positive VDREs is cooperative. The degree of cooperativity is highest with the calbindin VDRE compared with either the OSC-DRE or the MOP-DRE. This cooperativity is largely absent in the case of the negative element, the PTH-DRE. The VDR binds in order of decreasing affinity to PTH-DRE > OSC-DRE = MOP-DRE > CaBP-DRE. Thus, the greatest affinity is associated with the lowest degree of cooperativity. Further study has revealed that the PTH-VDRE actually consists of two repeat elements like all other VDREs and is not a single six-base sequence. A nuclear factor has also been found that binds downstream from the GGTTCA element in the PTH promoter. The binding site of this factor overlaps the PTH-DRE nucleotide sequence.
Department of Biochemistry, University of Wisconsin-Madison, 53706, USA.
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DeLuca
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D001667:Binding, Competitive; D064026:Calbindins; D002467:Cell Nucleus / Q000378:metabolism; D015342:DNA Probes; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D051379:Mice; D015345:Oligonucleotide Probes; D015675:Osteocalcin / Q000235:genetics*; D053495:Osteopontin; D010281:Parathyroid Hormone / Q000235:genetics*; D051381:Rats; D018167:Receptors, Calcitriol / Q000378:metabolism*; D064030:S100 Calcium Binding Protein G / Q000235:genetics*; D012795:Sialoglycoproteins / Q000235:genetics*; D014807:Vitamin D / Q000494:pharmacology*
D064026:Calbindins; D015342:DNA Probes; D004268:DNA-Binding Proteins; D015345:Oligonucleotide Probes; D010281:Parathyroid Hormone; D018167:Receptors, Calcitriol; D064030:S100 Calcium Binding Protein G; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; C506896:Spp1 protein, mouse; C506897:Spp1 protein, rat; D015675:Osteocalcin; D053495:Osteopontin; D014807:Vitamin D