Thyroid hormone nuclear receptors (TRs) are ligand-dependent transcription factors which regulate growth, differentiation and development and represent members of the steroid/retinoic acid superfamily. The two genes encoding TRs identified to date, TRα and TRβ, have been mapped to human chromosomes 17 and 3, respectively. TRs bind to thyroid hormone response elements(TREs) with half-site binding motifs in the orientation of palindromes, direct repeats or inverted palindromes. The affinities of binding are both variable and influenced differentially by 3,5,3'-triiodo-L-thyronine (T3). Transcriptional regulation by TRs is also modulated by heterodimerization with TR nuclear accessory proteins, the most extensively characterized of which are the retinoid X receptors (RXRα, RXRβ and RXRγ). To a certain extent, this activity is regulated by differential phosphorylation of TRs. Thus, not only are the biological activities of TRs regulated by heterodimerization with RXRs, but in addition, the gene regulatory activities of TRs are linked to other hormonal pathways.
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