PMID- 8011161 OWN - NLM STAT- MEDLINE DCOM- 19940727 LR - 20191101 IS - 1044-5498 (Print) IS - 1044-5498 (Linking) VI - 13 IP - 4 DP - 1994 Apr TI - Thyroid hormone and retinoic acid receptors form heterodimers with retinoid X receptors on direct repeats, palindromes, and inverted palindromes. PG - 333-41 AB - Thyroid hormone [3,5,3'-triiodothyronine (T3)] and retinoic acid (RA) receptors (T3Rs and RARs) are ligand-dependent transcription factors that regulate the transcription of T3- and RA-responsive genes, respectively, by binding to specific DNA sequences as homodimers or as heterodimers with retinoid X receptors (RXRs). These T3 and RA response elements are composed to two copies of the consensus half-site motif PuGGTCA. However, the specificity of the receptor complexes for response elements is dictated by their discrimination of the distance and the relative orientation of the half-sites. We found that both T3R-RXR and RAR-RXR heterodimers act functionally on all three response element configurations: direct repeats, palindromes, and inverted palindromes. On direct repeats, T3R-RXR and RAR-RXR heterodimers showed maximal trans-activation and in vitro DNA binding affinity when the core binding motifs were spaced by 4, 2, or 1 and 5 or 2 nucleotides, respectively, whereas both heterodimer types were mostly active on palindromes with no spacing. The binding of and trans-activation by T3R-RXR and RAR-RXR heterodimers on inverted palindromes was maximal with a half-site spacing of 5 or 6 and 7 or 8 nucleotides, respectively. Inverted palindromes, however, were the most specific response elements, because they were the only ones on which the activities of homodimeric and heterodimeric receptor complexes could be discriminated. We developed a model that suggests a sterical link between the optimal spacings observed with direct repeats and inverted palindromes. Taken together, the experimental data and the model provide further understanding of the regulation of T3-and retinoid-responsive genes. FAU - Schrader, M AU - Schrader M AD - Clinique de Dermatologie, Hopital Cantonal Universitaire, Geneve, Switzerland. FAU - Carlberg, C AU - Carlberg C LA - eng PT - Journal Article PL - United States TA - DNA Cell Biol JT - DNA and cell biology JID - 9004522 RN - 0 (Biopolymers) RN - 0 (Receptors, Cytoplasmic and Nuclear) RN - 0 (Receptors, Retinoic Acid) RN - 0 (Retinoid X Receptors) RN - 0 (Transcription Factors) RN - 06LU7C9H1V (Triiodothyronine) RN - 9007-49-2 (DNA) SB - IM MH - Animals MH - Base Sequence MH - Biopolymers MH - Cell Line MH - DNA/chemistry/*metabolism MH - Drosophila MH - Molecular Sequence Data MH - Nucleic Acid Conformation MH - Protein Binding MH - Receptors, Cytoplasmic and Nuclear/*metabolism MH - Receptors, Retinoic Acid/*metabolism MH - Repetitive Sequences, Nucleic Acid MH - Retinoid X Receptors MH - Transcription Factors/*metabolism MH - Transcriptional Activation MH - Triiodothyronine/*metabolism EDAT- 1994/04/01 00:00 MHDA- 1994/04/01 00:01 CRDT- 1994/04/01 00:00 PHST- 1994/04/01 00:00 [pubmed] PHST- 1994/04/01 00:01 [medline] PHST- 1994/04/01 00:00 [entrez] AID - 10.1089/dna.1994.13.333 [doi] PST - ppublish SO - DNA Cell Biol. 1994 Apr;13(4):333-41. doi: 10.1089/dna.1994.13.333.