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 homodim er or as a heterodimer with a number of other nuclear receptors. We pr eviously demonstrated that, in solution, RXR forms tetramers with a hi gh 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 (T REpa1) response elements. Binding of RXR tetramers to cognate DNA occu rs with a significantly higher affinity as compared with dimers. Ligan d binding by DNA-bound RXR tetramers results in their dissociation to DNA-bound dimers, a process that is completely reversed upon removal o f the ligand. Formation of stable tetramer-DNA complexes requires bind ing of two oligonucleotides/tetramer. It is proposed that ligand-depen dent modulation of the oligomeric state of RXR is a regulatory feature of this nuclear receptor.