YY1 regulates vitamin D receptor/retinoid X receptor mediated transactivation of the vitamin D responsive osteocalcin gene
Van Wijnen, Andre J.
Roberts, Stefan G. E.
Green, Michael R.
DeLuca, Hector F.
Lian, Jane B.
Stein, Gary S.
Stein, Janet L.
UMass Chan AffiliationsHoward Hughes Medical Institute, Program in Molecular Medicine
Department of Cell Biology
Department of Cell Biology
Graduate School of Biomedical Sciences
KeywordsAnimals; Binding Sites; Binding, Competitive; Bone and Bones; DNA-Binding Proteins; Erythroid-Specific DNA-Binding Factors; Models, Genetic; Nuclear Proteins; Osteocalcin; Osteosarcoma; Rats; Receptors, Calcitriol; Receptors, Retinoic Acid; Recombinant Proteins; Retinoid X Receptors; *Trans-Activation (Genetics); Transcription Factor TFIIB; Transcription Factors; Transfection; Tumor Cells, Cultured; Vitamin D; YY1 Transcription Factor
Medicine and Health Sciences
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AbstractThe responsiveness of genes to steroid hormones is principally mediated by functional interactions between DNA-bound hormone receptors and components of the transcriptional initiation machinery, including TATA-binding protein, TFIIB, or other RNA polymerase II associated factors. This interaction can be physiologically modulated by promoter context-specific transcription factors to facilitate optimal responsiveness of gene expression to hormone stimulation. One postulated regulatory mechanism involves the functional antagonism between hormone receptors and nonreceptor transcription factors interacting at the same hormone response element. Here we demonstrate that the multifunctional regulator YY1 represses 1,25-dihydroxyvitamin D3 (vitamin D)-induced transactivation of the bone tissue-specific osteocalcin gene. We identify YY1 recognition sequences within the vitamin D response element (VDRE) of the osteocalcin gene that are critical for YY1-dependent repression of vitamin D-enhanced promoter activity. We show that YY1 and vitamin D receptor (VDR)/retinoid X receptor heterodimers compete for binding at the osteocalcin VDRE. In addition, we find that YY1 interacts directly with TFIIB, and that one of the two tandemly repeated polypeptide regions of TFIIB spanning the basic domain is responsible for this interaction. TFIIB and VDR can also interact directly, and these factors synergize to mediate transactivation. Our results suggest that YY1 regulates vitamin D enhancement of osteocalcin gene transcription in vivo by interfering with the interactions of the VDR with both the VDRE and TFIIB.
Proc Natl Acad Sci U S A. 1997 Jan 7;94(1):121-6.
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/33794
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