Key points are not available for this paper at this time.
The carbonic anhydrase II gene, whose transcription is enhanced by 1,25-dihydroxyvitamin D3(1,25-(OH)2D3), encodes an important enzyme in bone-resorbing cells derived from the fusion of monocytic progenitors. We analyzed the 1,25-(OH)2D3-mediated activation of the avian gene by transient transfection assays with promoter/reporter constructs into HD11 chicken macrophages and by DNA mobility shift assays. Deletion and mobility shift analyses indicated that the −62/−29 region confers 1,25-(OH)2D3responsiveness and forms DNA-protein complexes. The addition of an anti-vitamin D receptor (VDR) antibody inhibited binding to this sequence, whereas anti-retinoid X receptor (RXR) antibody generated a lower mobility complex. Therefore, we concluded that this element binds a VDR·RXR heterodimer, but the addition of extra 1,25-(OH)2D3 had no effect on the formation of this complex. Moreover, the use of nuclear extracts from 1,25-(OH)2D3-treated macrophages led to the formation of an additional high mobility complex also composed of VDR·RXR heterodimer. Mutations provided evidence that the 1,25-(OH)2D3-mediated activation of the carbonic anhydrase II gene is mediated by VDR·RXR heterodimers bound to a DR3-type vitamin D response element with sequence AGGGCAtggAGTTCG. This vitamin D response element is also functional in the ROS 17/2.8 osteoblasts. The carbonic anhydrase II gene, whose transcription is enhanced by 1,25-dihydroxyvitamin D3(1,25-(OH)2D3), encodes an important enzyme in bone-resorbing cells derived from the fusion of monocytic progenitors. We analyzed the 1,25-(OH)2D3-mediated activation of the avian gene by transient transfection assays with promoter/reporter constructs into HD11 chicken macrophages and by DNA mobility shift assays. Deletion and mobility shift analyses indicated that the −62/−29 region confers 1,25-(OH)2D3responsiveness and forms DNA-protein complexes. The addition of an anti-vitamin D receptor (VDR) antibody inhibited binding to this sequence, whereas anti-retinoid X receptor (RXR) antibody generated a lower mobility complex. Therefore, we concluded that this element binds a VDR·RXR heterodimer, but the addition of extra 1,25-(OH)2D3 had no effect on the formation of this complex. Moreover, the use of nuclear extracts from 1,25-(OH)2D3-treated macrophages led to the formation of an additional high mobility complex also composed of VDR·RXR heterodimer. Mutations provided evidence that the 1,25-(OH)2D3-mediated activation of the carbonic anhydrase II gene is mediated by VDR·RXR heterodimers bound to a DR3-type vitamin D response element with sequence AGGGCAtggAGTTCG. This vitamin D response element is also functional in the ROS 17/2.8 osteoblasts. Recent work points to the complexity of the molecular mechanisms involved in the vitamin D3 signaling pathway. It has been known for some time that in addition to the binding of the vitamin D receptor (VDR) 1The abbreviations used are: VDR, vitamin D receptor; VDRE, vitamin D response element; RXR, retinoid X receptor; bp, base pair(s); DR3, direct repeats of two hexameric core binding sites spaced by three nucleotides; CAII, carbonic anhydrase II; 1,25-(OH)2D3, 1,25-dihydroxyvitamin D3; tk, thymidine kinase; CAT or Cat, chloramphenicol acetyltransferase; CMV, cytomegalovirus; EMSA, electrophoretic mobility shift assay; RAR, retinoic acid receptor; TR, thyroid hormone receptor; Mi, microphalmia transcription factor. 1The abbreviations used are: VDR, vitamin D receptor; VDRE, vitamin D response element; RXR, retinoid X receptor; bp, base pair(s); DR3, direct repeats of two hexameric core binding sites spaced by three nucleotides; CAII, carbonic anhydrase II; 1,25-(OH)2D3, 1,25-dihydroxyvitamin D3; tk, thymidine kinase; CAT or Cat, chloramphenicol acetyltransferase; CMV, cytomegalovirus; EMSA, electrophoretic mobility shift assay; RAR, retinoic acid receptor; TR, thyroid hormone receptor; Mi, microphalmia transcription factor. to certain vitamin D response elements (VDREs) as homodimer (3Carlberg C. Bendik I. Wyss A. Meier E. Sturzenbecker L.J. Grippo J.F. Hunziker W. Nature. 1993; 361: 657-660Crossref PubMed Scopus (500) Google Scholar, 4Schräder M. Becker-Andre M. Carlberg C. J. Biol. Chem. 1994; 269: 6444-6449Abstract Full Text PDF PubMed Google Scholar, 5Kim R.H. Li J.J. Ogata Y. Yamauchi M. Freedman L.P. Sodek J. Biochem. J. 1996; 318: 219-226Crossref PubMed Scopus (71) Google Scholar, 6Cheskis B. Freedman L.P. Mol. Cell. Biol. 1994; 14: 3329-3338Crossref PubMed Scopus (188) Google Scholar, 7Freedman L.P. Arce V. Fernandez R.P. Mol. Endocrinol. 1994; 8: 265-273Crossref PubMed Scopus (79) Google Scholar), the in vitro binding affinity of the VDR is enhanced by dimerization with accessory factors such as RXRs (8Cooney A.J. Tsai S.Y. O'Malley B.W. Tsai M.-J. Mol. Cell. Biol. 1992; 12: 4153-4163Crossref PubMed Scopus (335) Google Scholar, 9Kliewer S.A. Umesono K. Mangelsdorf D.J. Evans R.M. Nature. 1992; 355: 446-449Crossref PubMed Scopus (1232) Google Scholar, 10Carlberg C. Eur. J. Biochem. PubMed Scopus Google Scholar, M. R.P. W. Biochem. J. 1996; PubMed Scopus Google The response elements for from by the of base the hexameric repeats to the to K. Evans R.M. Cell. Full Text PDF PubMed Scopus Google Scholar, D.J. C. M. Umesono K. B. M. Evans R.M. Cell. Full Text PDF PubMed Scopus Google the to for VDR·RXR heterodimers direct repeats of two hexameric core binding sites spaced by three K. Evans R.M. Cell. Full Text PDF PubMed Scopus Google Scholar, C. Bendik I. Wyss A. Meier E. Sturzenbecker L.J. Grippo J.F. Hunziker W. Nature. 1993; 361: 657-660Crossref PubMed Scopus (500) Google The high of DR3-type by of some and C. Eur. J. Biochem. PubMed Scopus Google The has been to VDR with affinity (3Carlberg C. Bendik I. Wyss A. Meier E. Sturzenbecker L.J. Grippo J.F. Hunziker W. Nature. 1993; 361: 657-660Crossref PubMed Scopus (500) Google Scholar, 6Cheskis B. Freedman L.P. Mol. Cell. Biol. 1994; 14: 3329-3338Crossref PubMed Scopus (188) Google Scholar, J. Biochem. Mol. Biol. 1996; PubMed Scopus Google Scholar, M. M. PubMed Scopus Google but VDR·RXR heterodimers with high affinity (3Carlberg C. Bendik I. Wyss A. Meier E. Sturzenbecker L.J. Grippo J.F. Hunziker W. Nature. 1993; 361: 657-660Crossref PubMed Scopus (500) Google Scholar, 9Kliewer S.A. Umesono K. Mangelsdorf D.J. Evans R.M. Nature. 1992; 355: 446-449Crossref PubMed Scopus (1232) Google Scholar, M. M. J. A. PubMed Scopus Google Scholar, 1996; PubMed Scopus Google DR3-type elements also been in such as the gene A. PubMed Scopus Google Scholar, S.A. A. PubMed Scopus Google Scholar), the A. 1992; PubMed Scopus Google Scholar), the avian gene J. J. Biol. Chem. 1993; Full Text PDF PubMed Google Scholar), the gene C. A. 1994; PubMed Scopus Google Scholar, Y. K. M. M. Y. J. Biol. Chem. 1994; 269: Full Text PDF PubMed Google Scholar, 1994; PubMed Scopus Google Scholar), the avian carbonic anhydrase II gene I. A. Carlberg C. DNA Biol. 1994; PubMed Scopus Google Scholar), and M. M. M. Freedman L.P. 1996; PubMed Scopus Google the binding sites of the in of a sequence L.P. Arce V. Fernandez R.P. Mol. Endocrinol. 1994; 8: 265-273Crossref PubMed Scopus (79) Google Scholar, M. C. M. C. Mol. Cell. Endocrinol. PubMed Scopus Google Scholar, A. Freedman L.P. A. 1993; PubMed Scopus Google Scholar, M. M. M. 1994; PubMed Scopus Google of been in a of in of cells Biol. PubMed Scopus Google Scholar, J. 1993; PubMed Scopus Google Scholar), PubMed Scopus Google Scholar, M. M. PubMed Scopus Google Scholar, K. J. Biochem. 1993; Scopus Google Scholar), or cells A. PubMed Scopus Google Scholar, A. PubMed Scopus Google Scholar, J. Cell. Biochem. 1992; PubMed Scopus Google this of the mechanisms that to the forms of mediated by 1,25-(OH)2D3 is and bone-resorbing to the A. PubMed Scopus Google Scholar, B. J. 1992; PubMed Scopus Google Scholar), and is the of 1,25-(OH)2D3 A. J. A.J. A. PubMed Scopus Google Scholar, C. C. E. PubMed Scopus Google Scholar, J. 1993; PubMed Scopus Google Scholar, 1996; Google cells some such as acid and CAII, high in PubMed Scopus Google Scholar, Y. D.J. J. 1993; 8: PubMed Scopus Google Scholar), an important in the for and is of the factors for the in by a and a A. 1992; PubMed Scopus Google that the of in chicken macrophages C. C. E. PubMed Scopus Google the gene the in the chicken monocytic cells to into macrophages by and A. A. 1992; PubMed Scopus Google as as in the cells J. 1994; PubMed Scopus Google gene is also by thyroid hormone in cells B. J. Biol. Google Scholar), and in the avian been to the thyroid hormone of transcription C. C. J. J. J. M. PubMed Scopus Google A. J. J. 1994; Google we a and of the 1,25-(OH)2D3 to the thymidine in the and in cells I. A. Carlberg C. DNA Biol. 1994; PubMed Scopus Google This VDRE, bound by a VDR·RXR heterodimer, is functional in an avian the we for 1,25-(OH)2D3 of the gene transcription in We the of the avian in the chicken HD11 in nuclear and gene and in and in We for hormone response elements in this and an element 1,25-(OH)2D3-mediated activation to a region −62/−29 the The assays and by forms of this This VDRE, functional in HD11 and in ROS 17/2.8 has a with sequence and is bound by a by VDR and the or of this we that the chicken is in response to 1,25-(OH)2D3 in an avian We a in the for 1,25-(OH)2D3-mediated transfection assays in HD11 macrophages of or of the to a region involved in 1,25-(OH)2D3 DNA for gene and the of the to as the It is that the of 1,25-(OH)2D3 activation with the of the and the activation of with and analyses of the to a vitamin and of the We that this is functional in macrophages and is bound by a complex by a heterodimer. we that that binding to the vitamin activation in that the VDR has a binding for the direct composed of spaced by D.J. C. M. Umesono K. B. M. Evans R.M. Cell. Full Text PDF PubMed Scopus Google Scholar, C. Bendik I. Wyss A. Meier E. Sturzenbecker L.J. Grippo J.F. Hunziker W. Nature. 1993; 361: 657-660Crossref PubMed Scopus (500) Google Scholar, J. Biol. Chem. 1993; Full Text PDF PubMed Google Scholar, K. Y. M. Y. K. Mol. Cell. Biol. 1996; PubMed Scopus Google The of an of spaced by three with the sequence for the and for the the of the for the the of this and to VDR·RXR and a effect on the two hexameric of the element inhibited 1,25-(OH)2D3-mediated activation and of the that the of this is for binding the This is by the of a to for VDR binding with the sequence, whereas in the and in a in VDR binding to the with the important of the in the VDRE, we that the the for the binding of the complex on DNA or for the of known of the the of been It is of to that the hexameric core binding sites VDR and 1,25-(OH)2D3 We that the of the is the The the two binding of receptor of the complex bound to that RXRs to the binding in retinoic acid and thyroid hormone response elements as as in K. Evans R.M. Cell. Full Text PDF PubMed Scopus Google Scholar, 7Freedman L.P. Arce V. Fernandez R.P. Mol. Endocrinol. 1994; 8: 265-273Crossref PubMed Scopus (79) Google Scholar, M. C. M. C. Mol. Cell. Endocrinol. PubMed Scopus Google Scholar, A. Freedman L.P. A. 1993; PubMed Scopus Google Scholar, M. M. M. 1994; PubMed Scopus Google Scholar, Umesono K. Evans R.M. 1993; PubMed Scopus Google Scholar, A. 1993; PubMed Scopus Google PubMed Scopus Google that the in the of the is as we for the of this 1,25-(OH)2D3 and the binding of transcription factors to the the of the a high affinity binding whereas the sequence a VDR binding J. M. K. M. M. J. Biol. Chem. 1993; Full Text PDF PubMed Google with the with we by transient transfection that the vitamin D of the gene in VDR and we also in addition of with the and the of VDR·RXR heterodimers in the cells the Mol. Cell. Biol. PubMed Scopus Google two and on the with nuclear extracts from 1,25-(OH)2D3-treated HD11 whereas complex with extracts or and bound to this composed of VDR and We that in 1,25-(OH)2D3 a of the VDR·RXR to the formation of the whereas in the complex is This mobility complex by the binding of 1,25-(OH)2D3 to the VDR, the addition of extra 1,25-(OH)2D3 to the had no effect on the DNA binding affinity of the complex. such no in mobility or complex This that in binding of the is for the binding of to in to 1,25-(OH)2D3 the complex on DNA and in or the binding of a or a The two and by nuclear the of known or factors in addition to the VDR·RXR heterodimer. the transcription to with VDR J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar), has been as of in and to for the VDR to the M. C. C. D and of the of also involved in the binding of the VDR to the such as S.A. Nature. PubMed Scopus Google Scholar), D and of the of Scholar), E. C. M. 1994; PubMed Scopus Google Scholar, V. J. 14: PubMed Scopus Google Scholar), and S.A. Tsai S.Y. Tsai O'Malley B.W. PubMed Scopus Google accessory factors been to to the activation mediated by nuclear a direct with Mol. Cell. Biol. PubMed Scopus Google Scholar, D and of the of Scholar, E. C. M. 1994; PubMed Scopus Google Scholar, V. J. 14: PubMed Scopus Google Scholar, S.A. Tsai S.Y. Tsai O'Malley B.W. PubMed Scopus Google Scholar, M. A. M. Nature. PubMed Scopus Google Scholar, V. A. 1994; PubMed Scopus Google Scholar, PubMed Scopus Google The of the a transcription that 1,25-(OH)2D3-mediated by the and the transcription we the of this in a the ROS 17/2.8 analyses that the is also functional as a in the ROS 17/2.8 cells but the in this of the gene binding of the VDR·RXR heterodimer, is a and is functional in a the is functional in this the is in the the gene and is the region the Recent work points to the complexity of the molecular mechanisms involved in the vitamin D3 signaling pathway. It has been known for some time that in addition to the binding of the vitamin D receptor (VDR) 1The abbreviations used are: VDR, vitamin D receptor; VDRE, vitamin D response element; RXR, retinoid X receptor; bp, base pair(s); DR3, direct repeats of two hexameric core binding sites spaced by three nucleotides; CAII, carbonic anhydrase II; 1,25-(OH)2D3, 1,25-dihydroxyvitamin D3; tk, thymidine kinase; CAT or Cat, chloramphenicol acetyltransferase; CMV, cytomegalovirus; EMSA, electrophoretic mobility shift assay; RAR, retinoic acid receptor; TR, thyroid hormone receptor; Mi, microphalmia transcription factor. 1The abbreviations used are: VDR, vitamin D receptor; VDRE, vitamin D response element; RXR, retinoid X receptor; bp, base pair(s); DR3, direct repeats of two hexameric core binding sites spaced by three nucleotides; CAII, carbonic anhydrase II; 1,25-(OH)2D3, 1,25-dihydroxyvitamin D3; tk, thymidine kinase; CAT or Cat, chloramphenicol acetyltransferase; CMV, cytomegalovirus; EMSA, electrophoretic mobility shift assay; RAR, retinoic acid receptor; TR, thyroid hormone receptor; Mi, microphalmia transcription factor. to certain vitamin D response elements (VDREs) as homodimer (3Carlberg C. Bendik I. Wyss A. Meier E. Sturzenbecker L.J. Grippo J.F. Hunziker W. Nature. 1993; 361: 657-660Crossref PubMed Scopus (500) Google Scholar, 4Schräder M. Becker-Andre M. Carlberg C. J. Biol. Chem. 1994; 269: 6444-6449Abstract Full Text PDF PubMed Google Scholar, 5Kim R.H. Li J.J. Ogata Y. Yamauchi M. Freedman L.P. Sodek J. Biochem. J. 1996; 318: 219-226Crossref PubMed Scopus (71) Google Scholar, 6Cheskis B. Freedman L.P. Mol. Cell. Biol. 1994; 14: 3329-3338Crossref PubMed Scopus (188) Google Scholar, 7Freedman L.P. Arce V. Fernandez R.P. Mol. Endocrinol. 1994; 8: 265-273Crossref PubMed Scopus (79) Google Scholar), the in vitro binding affinity of the VDR is enhanced by dimerization with accessory factors such as RXRs (8Cooney A.J. Tsai S.Y. O'Malley B.W. Tsai M.-J. Mol. Cell. Biol. 1992; 12: 4153-4163Crossref PubMed Scopus (335) Google Scholar, 9Kliewer S.A. Umesono K. Mangelsdorf D.J. Evans R.M. Nature. 1992; 355: 446-449Crossref PubMed Scopus (1232) Google Scholar, 10Carlberg C. Eur. J. Biochem. PubMed Scopus Google Scholar, M. R.P. W. Biochem. J. 1996; PubMed Scopus Google The response elements for from by the of base the hexameric repeats to the to K. Evans R.M. Cell. Full Text PDF PubMed Scopus Google Scholar, D.J. C. M. Umesono K. B. M. Evans R.M. Cell. Full Text PDF PubMed Scopus Google the to for VDR·RXR heterodimers direct repeats of two hexameric core binding sites spaced by three K. Evans R.M. Cell. Full Text PDF PubMed Scopus Google Scholar, C. Bendik I. Wyss A. Meier E. Sturzenbecker L.J. Grippo J.F. Hunziker W. Nature. 1993; 361: 657-660Crossref PubMed Scopus (500) Google The high of DR3-type by of some and C. Eur. J. Biochem. PubMed Scopus Google The has been to VDR with affinity (3Carlberg C. Bendik I. Wyss A. Meier E. Sturzenbecker L.J. Grippo J.F. Hunziker W. Nature. 1993; 361: 657-660Crossref PubMed Scopus (500) Google Scholar, 6Cheskis B. Freedman L.P. Mol. Cell. Biol. 1994; 14: 3329-3338Crossref PubMed Scopus (188) Google Scholar, J. Biochem. Mol. Biol. 1996; PubMed Scopus Google Scholar, M. M. PubMed Scopus Google but VDR·RXR heterodimers with high affinity (3Carlberg C. Bendik I. Wyss A. Meier E. Sturzenbecker L.J. Grippo J.F. Hunziker W. Nature. 1993; 361: 657-660Crossref PubMed Scopus (500) Google Scholar, 9Kliewer S.A. Umesono K. Mangelsdorf D.J. Evans R.M. Nature. 1992; 355: 446-449Crossref PubMed Scopus (1232) Google Scholar, M. M. J. A. PubMed Scopus Google Scholar, 1996; PubMed Scopus Google DR3-type elements also been in such as the gene A. PubMed Scopus Google Scholar, S.A. A. PubMed Scopus Google Scholar), the A. 1992; PubMed Scopus Google Scholar), the avian gene J. J. Biol. Chem. 1993; Full Text PDF PubMed Google Scholar), the gene C. A. 1994; PubMed Scopus Google Scholar, Y. K. M. M. Y. J. Biol. Chem. 1994; 269: Full Text PDF PubMed Google Scholar, 1994; PubMed Scopus Google Scholar), the avian carbonic anhydrase II gene I. A. Carlberg C. DNA Biol. 1994; PubMed Scopus Google Scholar), and M. M. M. Freedman L.P. 1996; PubMed Scopus Google the binding sites of the in of a sequence L.P. Arce V. Fernandez R.P. Mol. Endocrinol. 1994; 8: 265-273Crossref PubMed Scopus (79) Google Scholar, M. C. M. C. Mol. Cell. Endocrinol. PubMed Scopus Google Scholar, A. Freedman L.P. A. 1993; PubMed Scopus Google Scholar, M. M. M. 1994; PubMed Scopus Google The of been in a of in of cells Biol. PubMed Scopus Google Scholar, J. 1993; PubMed Scopus Google Scholar), PubMed Scopus Google Scholar, M. M. PubMed Scopus Google Scholar, K. J. Biochem. 1993; Scopus Google Scholar), or cells A. PubMed Scopus Google Scholar, A. PubMed Scopus Google Scholar, J. Cell. Biochem. 1992; PubMed Scopus Google this of the mechanisms that to the forms of mediated by 1,25-(OH)2D3 is and bone-resorbing to the A. PubMed Scopus Google Scholar, B. J. 1992; PubMed Scopus Google Scholar), and is the of 1,25-(OH)2D3 A. J. A.J. A. PubMed Scopus Google Scholar, C. C. E. PubMed Scopus Google Scholar, J. 1993; PubMed Scopus Google Scholar, 1996; Google cells some such as acid and CAII, high in PubMed Scopus Google Scholar, Y. D.J. J. 1993; 8: PubMed Scopus Google Scholar), an important in the for and is of the factors for the in by a and a A. 1992; PubMed Scopus Google We that the of in chicken macrophages C. C. E. PubMed Scopus Google the gene the in the chicken monocytic cells to into macrophages by and A. A. 1992; PubMed Scopus Google as as in the cells J. 1994; PubMed Scopus Google gene is also by thyroid hormone in cells B. J. Biol. Google Scholar), and in the avian been to the thyroid hormone of transcription C. C. J. J. J. M. PubMed Scopus Google A. J. J. 1994; Google we a and of the 1,25-(OH)2D3 to the thymidine in the and in cells I. A. Carlberg C. DNA Biol. 1994; PubMed Scopus Google This VDRE, bound by a VDR·RXR heterodimer, is functional in an avian the we for 1,25-(OH)2D3 of the gene transcription in We the of the avian in the chicken HD11 in nuclear and gene and in and in We for hormone response elements in this and an element 1,25-(OH)2D3-mediated activation to a region −62/−29 the The assays and by forms of this This VDRE, functional in HD11 and in ROS 17/2.8 has a with sequence and is bound by a by VDR and the or of this we that the chicken is in response to 1,25-(OH)2D3 in an avian We a in the for 1,25-(OH)2D3-mediated transfection assays in HD11 macrophages of or of the to a region involved in 1,25-(OH)2D3 DNA for gene and the of the to as the It is that the of 1,25-(OH)2D3 activation with the of the and the activation of with and analyses of the to a vitamin and of the We that this is functional in macrophages and is bound by a complex by a heterodimer. we that that binding to the vitamin activation in that the VDR has a binding for the direct composed of spaced by D.J. C. M. Umesono K. B. M. Evans R.M. Cell. Full Text PDF PubMed Scopus Google Scholar, C. Bendik I. Wyss A. Meier E. Sturzenbecker L.J. Grippo J.F. Hunziker W. Nature. 1993; 361: 657-660Crossref PubMed Scopus (500) Google Scholar, J. Biol. Chem. 1993; Full Text PDF PubMed Google Scholar, K. Y. M. Y. K. Mol. Cell. Biol. 1996; PubMed Scopus Google The of an of spaced by three with the sequence for the and for the the of the for the the of this and to VDR·RXR and a effect on the two hexameric of the element inhibited 1,25-(OH)2D3-mediated activation and of the that the of this is for binding the This is by the of a to for VDR binding with the sequence, whereas in the and in a in VDR binding to the with the important of the in the VDRE, we that the the for the binding of the complex on DNA or for the of known of the the of been It is of to that the hexameric core binding sites VDR and 1,25-(OH)2D3 We that the of the is the The the two binding of receptor of the complex bound to that RXRs to the binding in retinoic acid and thyroid hormone response elements as as in K. Evans R.M. Cell. Full Text PDF PubMed Scopus Google Scholar, 7Freedman L.P. Arce V. Fernandez R.P. Mol. Endocrinol. 1994; 8: 265-273Crossref PubMed Scopus (79) Google Scholar, M. C. M. C. Mol. Cell. Endocrinol. PubMed Scopus Google Scholar, A. Freedman L.P. A. 1993; PubMed Scopus Google Scholar, M. M. M. 1994; PubMed Scopus Google Scholar, Umesono K. Evans R.M. 1993; PubMed Scopus Google Scholar, A. 1993; PubMed Scopus Google PubMed Scopus Google that the in the of the is as we for the of this 1,25-(OH)2D3 and the binding of transcription factors to the the of the a high affinity binding whereas the sequence a VDR binding J. M. K. M. M. J. Biol. Chem. 1993; Full Text PDF PubMed Google with the with we by transient transfection that the vitamin D of the gene in VDR and we also in addition of with the and the of VDR·RXR heterodimers in the cells the Mol. Cell. Biol. PubMed Scopus Google two and on the with nuclear extracts from 1,25-(OH)2D3-treated HD11 whereas complex with extracts or and bound to this composed of VDR and We that in 1,25-(OH)2D3 a of the VDR·RXR to the formation of the whereas in the complex is This mobility complex by the binding of 1,25-(OH)2D3 to the VDR, the addition of extra 1,25-(OH)2D3 to the had no effect on the DNA binding affinity of the complex. such no in mobility or complex This that in binding of the is for the binding of to in to 1,25-(OH)2D3 the complex on DNA and in or the binding of a or a The two and by nuclear the of known or factors in addition to the VDR·RXR heterodimer. the transcription to with VDR J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar), has been as of in and to for the VDR to the M. C. C. D and of the of also involved in the binding of the VDR to the such as S.A. Nature. PubMed Scopus Google Scholar), D and of the of Scholar), E. C. M. 1994; PubMed Scopus Google Scholar, V. J. 14: PubMed Scopus Google Scholar), and S.A. Tsai S.Y. Tsai O'Malley B.W. PubMed Scopus Google accessory factors been to to the activation mediated by nuclear a direct with Mol. Cell. Biol. PubMed Scopus Google Scholar, D and of the of Scholar, E. C. M. 1994; PubMed Scopus Google Scholar, V. J. 14: PubMed Scopus Google Scholar, S.A. Tsai S.Y. Tsai O'Malley B.W. PubMed Scopus Google Scholar, M. A. M. Nature. PubMed Scopus Google Scholar, V. A. 1994; PubMed Scopus Google Scholar, PubMed Scopus Google The of the a transcription that 1,25-(OH)2D3-mediated by the and the transcription we the of this in a the ROS 17/2.8 analyses that the is also functional as a in the ROS 17/2.8 cells but the in this of the gene binding of the VDR·RXR heterodimer, is a and is functional in a the is functional in this the is in the the gene and is the region the this we that the chicken is in response to 1,25-(OH)2D3 in an avian We a in the for 1,25-(OH)2D3-mediated transfection assays in HD11 macrophages of or of the to a region involved in 1,25-(OH)2D3 DNA for gene and the of the to as the It is that the of 1,25-(OH)2D3 activation with the of the and the activation of with and analyses of the to a vitamin and of the We that this is functional in macrophages and is bound by a complex by a heterodimer. we that that binding to the vitamin activation in that the VDR has a binding for the direct composed of spaced by D.J. C. M. Umesono K. B. M. Evans R.M. Cell. Full Text PDF PubMed Scopus Google Scholar, C. Bendik I. Wyss A. Meier E. Sturzenbecker L.J. Grippo J.F. Hunziker W. Nature. 1993; 361: 657-660Crossref PubMed Scopus (500) Google Scholar, J. Biol. Chem. 1993; Full Text PDF PubMed Google Scholar, K. Y. M. Y. K. Mol. Cell. Biol. 1996; PubMed Scopus Google The of an of spaced by three with the sequence for the and for the the of the for the the of this and to VDR·RXR and a effect on the two hexameric of the element inhibited 1,25-(OH)2D3-mediated activation and of the that the of this is for binding the This is by the of a to for VDR binding with the sequence, whereas in the and in a in VDR binding to the with the important of the in the VDRE, we that the the for the binding of the complex on DNA or for the The of known of the the of been It is of to that the hexameric core binding sites VDR and 1,25-(OH)2D3 We that the of the is the The the two binding of receptor of the complex bound to that RXRs to the binding in retinoic acid and thyroid hormone response elements as as in K. Evans R.M. Cell. Full Text PDF PubMed Scopus Google Scholar, 7Freedman L.P. Arce V. Fernandez R.P. Mol. Endocrinol. 1994; 8: 265-273Crossref PubMed Scopus (79) Google Scholar, M. C. M. C. Mol. Cell. Endocrinol. PubMed Scopus Google Scholar, A. Freedman L.P. A. 1993; PubMed Scopus Google Scholar, M. M. M. 1994; PubMed Scopus Google Scholar, Umesono K. Evans R.M. 1993; PubMed Scopus Google Scholar, A. 1993; PubMed Scopus Google PubMed Scopus Google that the in the of the is as we for the of this 1,25-(OH)2D3 and the binding of transcription factors to the the of the a high affinity binding whereas the sequence a VDR binding J. M. K. M. M. J. Biol. Chem. 1993; Full Text PDF PubMed Google with the with we by transient transfection that the vitamin D of the gene in VDR and we also in addition of with the and the of VDR·RXR heterodimers in the cells the Mol. Cell. Biol. PubMed Scopus Google two and on the with nuclear extracts from 1,25-(OH)2D3-treated HD11 whereas complex with extracts or and bound to this composed of VDR and We that in 1,25-(OH)2D3 a of the VDR·RXR to the formation of the whereas in the complex is This mobility complex by the binding of 1,25-(OH)2D3 to the VDR, the addition of extra 1,25-(OH)2D3 to the had no effect on the DNA binding affinity of the complex. such no in mobility or complex This that in binding of the is for the binding of to in to 1,25-(OH)2D3 the complex on DNA and in or the binding of a or a The two and by nuclear the of known or factors in addition to the VDR·RXR heterodimer. the transcription to with VDR J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar), has been as of in and to for the VDR to the M. C. C. D and of the of also involved in the binding of the VDR to the such as S.A. Nature. PubMed Scopus Google Scholar), D and of the of Scholar), E. C. M. 1994; PubMed Scopus Google Scholar, V. J. 14: PubMed Scopus Google Scholar), and S.A. Tsai S.Y. Tsai O'Malley B.W. PubMed Scopus Google accessory factors been to to the activation mediated by nuclear a direct with Mol. Cell. Biol. PubMed Scopus Google Scholar, D and of the of Scholar, E. C. M. 1994; PubMed Scopus Google Scholar, V. J. 14: PubMed Scopus Google Scholar, S.A. Tsai S.Y. Tsai O'Malley B.W. PubMed Scopus Google Scholar, M. A. M. Nature. PubMed Scopus Google Scholar, V. A. 1994; PubMed Scopus Google Scholar, PubMed Scopus Google The of the a transcription that 1,25-(OH)2D3-mediated by the and the transcription we the of this in a the ROS 17/2.8 analyses that the is also functional as a in the ROS 17/2.8 cells but the in this of the gene binding of the VDR·RXR heterodimer, is a and is functional in a the is functional in this the is in the the gene and is the region the We for the and for and M. for We also A. and J. for and for of the
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