TY - JOUR
T1 - Competition for a unique response element mediates retinoic acid inhibition of vitamin D3-stimulated transcription
AU - Cao, Xu
AU - Teitelbaum, Steven L.
AU - Zhu, Hui Jun
AU - Zhang, Liming
AU - Feng, Xu
AU - Patrick Ross, F.
PY - 1996
Y1 - 1996
N2 - We have identified a novel steroid hormone response element in the avian β3 integrin promoter. This sequence, comprising three hexameric direct repeat half-sites separated by nine and three nucleotides binds vitamin D receptor (VDR)-retinoid X receptor (RXR) and retinoic acid receptor (RAR)- RXR heterodimers. VDR-RXR binds direct repeats separated by three base pairs, and HAR-RXR recognizes half-sites separated by nine bases, whereas the central half-site interacts with both heterodimers. Retinoic acid and 1,25- dihydroxyvitamin D3 activate both a genomic fragment including the transcriptional start site and an oligonucleotide containing the three repeats, linked to a heterologous promoter. Co-addition of the steroids produces neither synergy nor an additive effect; rather the result equals that for retinoic acid alone. Scatchard analysis demonstrates that RAR-RXR has greater affinity than VDR-RXR for the composite element. Based on these findings we propose a model in which there is specific, polarity-defined binding of VDR-RXR and RAR-RXR to three half-sites, which form two overlapping steroid response elements, with the central half-site common to both. Our results identify a novel mechanism by which one steroid hormone can modulate the activity of a second, by competing for a shared half-site in a composite response element.
AB - We have identified a novel steroid hormone response element in the avian β3 integrin promoter. This sequence, comprising three hexameric direct repeat half-sites separated by nine and three nucleotides binds vitamin D receptor (VDR)-retinoid X receptor (RXR) and retinoic acid receptor (RAR)- RXR heterodimers. VDR-RXR binds direct repeats separated by three base pairs, and HAR-RXR recognizes half-sites separated by nine bases, whereas the central half-site interacts with both heterodimers. Retinoic acid and 1,25- dihydroxyvitamin D3 activate both a genomic fragment including the transcriptional start site and an oligonucleotide containing the three repeats, linked to a heterologous promoter. Co-addition of the steroids produces neither synergy nor an additive effect; rather the result equals that for retinoic acid alone. Scatchard analysis demonstrates that RAR-RXR has greater affinity than VDR-RXR for the composite element. Based on these findings we propose a model in which there is specific, polarity-defined binding of VDR-RXR and RAR-RXR to three half-sites, which form two overlapping steroid response elements, with the central half-site common to both. Our results identify a novel mechanism by which one steroid hormone can modulate the activity of a second, by competing for a shared half-site in a composite response element.
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U2 - 10.1074/jbc.271.34.20650
DO - 10.1074/jbc.271.34.20650
M3 - Article
C2 - 8702813
AN - SCOPUS:0029812066
SN - 0021-9258
VL - 271
SP - 20650
EP - 20654
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 34
ER -