PMID- 7916971 OWN - NLM STAT- MEDLINE DCOM- 19941117 LR - 20191023 IS - 0952-5041 (Print) IS - 0952-5041 (Linking) VI - 12 IP - 3 DP - 1994 Jun TI - Response element selectivity for heterodimerization of vitamin D receptors with retinoic acid and retinoid X receptors. PG - 327-39 AB - The transcription of vitamin D (VD) responsive genes is regulated by three different nuclear signalling pathways mediated by homodimers of VD receptors (VDRs), heterodimers of VDRs and retinoid X receptors (RXRs) and heterodimers of VDRs with retinoic acid receptors (RARs), Here, the in vitro DNA-binding affinity of all three receptor complexes was shown to be enhanced by the presence of VD. However, the specificity of the three pathways was dictated by the differential affinities of the receptor complexes for VD response elements. Potential response elements were distinguished by the sequence, the separation and the relative orientation of the hexameric core binding motifs. It was found that both VDR-RAR and VDR-RXR heterodimers act functionally on all three response element configurations: direct repeats, palindromes and inverted palindromes. With direct repeats, neither heterodimer type showed a preference for any of the three principal core motifs, (A/G)GGTGA, (A/G)GGTCA and (A/G)GTTCA. However, while they did exhibit preferences for core motifs in palindromes, the spacing requirements were identical for both complexes. Inverted palindromes, however, formed the most specific response elements. A simple model explains a steric link between the optimal spacing of direct repeats and that of inverted palindromes. Taken together, the experimental data and the model provide further criteria for the screening of VD responsive genes. FAU - Schrader, M AU - Schrader M AD - Clinique de Dermatologie, Hopital Cantonal Universitaire, Geneve, Switzerland. FAU - Muller, K M AU - Muller KM FAU - Becker-Andre, M AU - Becker-Andre M FAU - Carlberg, C AU - Carlberg C LA - eng PT - Comparative Study PT - Journal Article PL - England TA - J Mol Endocrinol JT - Journal of molecular endocrinology JID - 8902617 RN - 0 (DNA, Recombinant) RN - 0 (Receptors, Calcitriol) RN - 0 (Receptors, Cytoplasmic and Nuclear) RN - 0 (Receptors, Retinoic Acid) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Retinoid X Receptors) RN - 0 (Transcription Factors) RN - 1406-16-2 (Vitamin D) SB - IM MH - Animals MH - Base Sequence MH - Binding, Competitive MH - Cell Line MH - DNA, Recombinant/genetics/metabolism MH - Drosophila MH - *Gene Expression Regulation/drug effects MH - Genes, Synthetic MH - Molecular Sequence Data MH - Protein Binding MH - *Protein Conformation MH - Receptors, Calcitriol/chemistry/*physiology MH - Receptors, Cytoplasmic and Nuclear/chemistry/*physiology MH - Receptors, Retinoic Acid/chemistry/*physiology MH - Recombinant Fusion Proteins/biosynthesis MH - *Regulatory Sequences, Nucleic Acid MH - Repetitive Sequences, Nucleic Acid MH - Retinoid X Receptors MH - *Transcription Factors MH - Vitamin D/*pharmacology EDAT- 1994/06/01 00:00 MHDA- 1994/06/01 00:01 CRDT- 1994/06/01 00:00 PHST- 1994/06/01 00:00 [pubmed] PHST- 1994/06/01 00:01 [medline] PHST- 1994/06/01 00:00 [entrez] AID - 10.1677/jme.0.0120327 [doi] PST - ppublish SO - J Mol Endocrinol. 1994 Jun;12(3):327-39. doi: 10.1677/jme.0.0120327.