RXR-independent action of the receptors for thyroid hormone, retinoid acid and vitamin D on inverted palindromes.

Hydrophobic ligands, like all-trans and 9-cis retinoic acid (RA), 3,5,3'-triiodothyronine (T3) and 1,25-dihydroxy-cholecalciferol (VD), mediate their biological response by binding to their respective nuclear receptors (RARs, RXRs, T3Rs and VDRs) which are members of the steroid receptor superfamily. These ligand-dependent transcription factors bind as dimers to specific DNA sequences known as hormone response elements. The specificity of the receptor complexes for response elements is dictated by their discrimination of half-site sequences, their distance and their relative orientation. Here, RXR-independent transactivation of VDRs, T3Rs, and RARs and their in vitro DNA binding to various response elements were investigated. The data indicate that functional response elements can consist of direct repeats, palindromes and inverted palindromes. A sterical link between the optimal spacers of direct repeats and inverted palindromes is suggested.