Cooperative formation of high-order oligomers by retinoid X receptors: an unexpected mode of DNA recognition.
Nuclear hormone receptors are ligand-regulated transcription factors that function in metazoan homeostasis and differentiation. We report here that DNA recognition by at least one class of nuclear receptors, the retinoid X receptors (RXRs), can occur through an unanticipated mechanism involving the cooperative formation of protein tetramers and other high-order oligomers. Formation of these oligomeric complexes enables RXRs alpha and gamma, but not beta, to efficiently regulate transcription through response elements poorly recognized by RXR dimers. Thus, oligomer formation plays an important role in determining the specificity of DNA recognition by nuclear receptors and contributes to isoform-dependent differences in gene regulation.
Section of Microbiology, University of California at Davis 95616.
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Privalsky
D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000378:metabolism*; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D008969:Molecular Sequence Data; D009841:Oligonucleotides; D011485:Protein Binding; D011487:Protein Conformation; D051381:Rats; D018168:Receptors, Retinoic Acid / Q000378:metabolism*; D012045:Regulatory Sequences, Nucleic Acid; D012091:Repetitive Sequences, Nucleic Acid; D047488:Retinoid X Receptors; D012177:Retinol-Binding Proteins / Q000378:metabolism; D054840:Retinol-Binding Proteins, Cellular; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000378:metabolism*
D009841:Oligonucleotides; C518459:RBP2 protein, human; C518461:Rbp2 protein, rat; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D012177:Retinol-Binding Proteins; D054840:Retinol-Binding Proteins, Cellular; D014157:Transcription Factors; D004247:DNA