title: Heterodimers of retinoic acid receptors and thyroid hormone receptors display unique combinatorial regulatory properties.
abstract: Nuclear receptors are ligand-regulated transcription factors that regulate key aspects of metazoan development, differentiation, and homeostasis. Nuclear receptors recognize target genes by binding to specific DNA recognition sequences, denoted hormone response elements (HREs). Many nuclear receptors can recognize HREs as either homodimers or heterodimers. Retinoid X receptors (RXRs), in particular, serve as important heterodimer partners for many other nuclear receptors, including thyroid hormone receptors (TRs), and RXR/TR heterodimers have been proposed to be the primary mediators of target gene regulation by T3 hormone. Here, we report that the retinoic acid receptors (RARs), a distinct class of nuclear receptors, are also efficient heterodimer partners for TRs. These RAR/TR heterodimers form with similar affinities as RXR/TR heterodimers on an assortment of consensus and natural HREs, and preferentially assemble with the RAR partner 5' of the TR moiety. The corepressor and coactivator recruitment properties of these RAR/TR heterodimers and their transcriptional activities in vivo are distinct from those observed with the corresponding RXR heterodimers. Our studies indicate that RXRs are not unique in their ability to partner with TRs, and that RARs can also serve as robust heterodimer partners and combinatorial regulators of T3-modulated gene expression.
authors.affiliation: Section of Microbiology, One Shields Avenue, University of California at Davis, Davis, California 95616, USA.
authors.forename: Sangho
authors.initials: S
authors.lastname: Lee
authors.forename: Martin L
authors.initials: ML
authors.lastname: Privalsky
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism*; D019281:Dimerization; D017930:Genes, Reporter; D051548:Histone Acetyltransferases; D006801:Humans; D056920:Nuclear Receptor Coactivator 1; D056921:Nuclear Receptor Coactivator 3; D018168:Receptors, Retinoic Acid / Q000378:metabolism*; D020218:Response Elements; D000072482:Retinoic Acid Receptor alpha; D047491:Retinoid X Receptor gamma / Q000378:metabolism*; D037021:Thyroid Hormone Receptors alpha / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation; D014284:Triiodothyronine / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C000607071:RARA protein, human; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D047491:Retinoid X Receptor gamma; D037021:Thyroid Hormone Receptors alpha; D014157:Transcription Factors; D014284:Triiodothyronine; D051548:Histone Acetyltransferases; C538859:NCOA1 protein, human; D056920:Nuclear Receptor Coactivator 1; D056921:Nuclear Receptor Coactivator 3