Triiodothyronine (T3) differentially affects T3-receptor/retinoic acid receptor and T3-receptor/retinoid X receptor heterodimer binding to DNA.
Thyroid hormone receptor (TR) heterodimerizes with retinoic acid receptor (RAR), retinoid X receptor (RXR), and triiodothyronine receptor auxiliary protein (TRAP) on natural and synthetic hormone response elements. Recently we showed that triiodothyronine (T3) decreased TR homodimer, but not TR/TRAP heterodimer, binding to several thyroid hormone response elements (TREs). The effect of ligand on TR/RAR and TR/RXR heterodimer binding to DNA is not known. In this study, we showed that TR formed heterodimers with RAR and RXR on a retinoic acid (RA) response element and two TREs. Surprisingly, T3, but not RA, decreased TR/RAR heterodimer binding to DNA. In contrast, T3, all-trans-RA, or 9-cis-RA did not affect TR/RXR binding to DNA. This finding suggests that TR/RXR heterodimer is a stable receptor complex that remains bound to response elements in the presence of ligand and therefore may be a receptor complex involved in T3-regulated transcription.
Yen
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PM
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115.
Sugawara
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Chin
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D000818:Animals; D002352:Carrier Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D015342:DNA Probes; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D046911:Macromolecular Substances; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism*; D014176:Protein Biosynthesis; D051381:Rats; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000187:drug effects / Q000378:metabolism; D047488:Retinoid X Receptors; D014157:Transcription Factors; D014158:Transcription, Genetic / Q000187:drug effects; D014212:Tretinoin / Q000378:metabolism; D014284:Triiodothyronine / Q000494:pharmacology*
D002352:Carrier Proteins; D015342:DNA Probes; D004268:DNA-Binding Proteins; D046911:Macromolecular Substances; D009687:Nuclear Proteins; D011956:Receptors, Cell Surface; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D011994:Recombinant Proteins; D047488:Retinoid X Receptors; D014157:Transcription Factors; D014284:Triiodothyronine; D014212:Tretinoin; D004247:DNA