AP-1 and vitamin D receptor (VDR) signaling pathways converge at the rat osteocalcin VDR element: requirement for the internal activating protein-1 site for vitamin D-mediated trans-activation
McCabe, Laura R.
Van Wijnen, Andre J.
Stein, Gary S.
Lian, Jane B.
Stein, Janet L.
UMass Chan AffiliationsDepartment of Cell Biology
Graduate School of Biomedical Sciences
Document TypeJournal Article
KeywordsAnimals; DNA; Humans; Inhibitor of Apoptosis Proteins; Osteocalcin; Promoter Regions (Genetics); Rats; Receptors, Calcitriol; Receptors, Retinoic Acid; Retinoid X Receptors; *Signal Transduction; Trans-Activation (Genetics); Transcription Factor AP-1; Transcription Factors; Transcription, Genetic; Transfection; Tumor Cells, Cultured; Viral Proteins
Medicine and Health Sciences
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AbstractResponsiveness of genes to steroid hormones is a complex process involving synergistic and/or antagonistic interactions between specific receptors and other nonreceptor transcription factors. Thus, DNA recognition elements for steroid hormone receptors are often located among binding sites for other trans-acting factors. The hormonal form of vitamin D, 1,25-dihydroxyvitamin D3, stimulates transcription of the tissue-specific osteocalcin (OC) gene in osteoblastic cells. The rat OC vitamin D response element contains an internal acitvating protein-1 (AP-1) site. Here, we report for the first time that this AP-1 site is critical for the transcriptional enhancement of rat osteocalcin gene expression mediated by vitamin D. Precise mutations were introduced either in the steroid half-elements or in the internal AP-1 sequences. One mutation within the internal AP-1 site retained vitamin D receptor/retinoid X receptor binding equivalent to that of the wild-type sequence, but resulted in complete loss of vitamin D inducibility of the OC promoter. These results suggest a functional interaction between the hormone receptor and nuclear oncoproteins at the rat OC vitamin D response element. This cooperation of activities may have important consequences in physiological regulation of osteocalcin transcription during osteoblast differentiation and bone tissue development in vivo.
Endocrinology. 1999 Jan;140(1):63-70.
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/33947