The DNA Binding Pattern of the Retinoid X Receptor Is Regulated by Ligand-dependent Modulation of Its Oligomeric State

The retinoid X receptor (RXR) regulates target gene transcription via its association with cognate DNA response elements either as a homodimer or as a heterodimer with a number of other nuclear receptors. We previously demonstrated that, in solution, RXR forms tetramers with a high affinity and that ligand binding leads to dissociation of receptor tetramers to smaller species. Here it is shown that RXR tetramers form stable complexes with direct repeats (DR-1 or DR-5) or palindromic (TREpal) response elements. Binding of RXR tetramers to cognate DNA occurs with a significantly higher affinity as compared with dimers. Ligand binding by DNA-bound RXR tetramers results in their dissociation to DNA-bound dimers, a process that is completely reversed upon removal of the ligand. Formation of stable tetramer-DNA complexes requires binding of two oligonucleotides/tetramer. It is proposed that ligand-dependent modulation of the oligomeric state of RXR is a regulatory feature of this nuclear receptor.