title: The DNA binding pattern of the retinoid X receptor is regulated by ligand-dependent modulation of its oligomeric state.
abstract: 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.
authors.affiliation: Cornell University, Division of Nutritional Sciences, Savage Hall, Ithaca, New York 14853-6301, USA.
authors.forename: S
authors.initials: S
authors.lastname: Kersten
authors.forename: H
authors.initials: H
authors.lastname: Gronemeyer
authors.forename: N
authors.initials: N
authors.lastname: Noy
mesh_terms: D000818:Animals; D019556:COS Cells; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004926:Escherichia coli; D007700:Kinetics; D009687:Nuclear Proteins / Q000378:metabolism*; D011487:Protein Conformation; D018168:Receptors, Retinoic Acid / Q000378:metabolism*; D047488:Retinoid X Receptors; D018411:Spodoptera; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors; D004247:DNA