Yen P M, Darling D S, Carter R L, Forgione M, Umeda P K, Chin W W
Department of Medicine, Brigham and Women's Hospital, Howard Hughes Medical Institute, Boston, Massachusetts 02115.
J Biol Chem. 1992 Feb 25;267(6):3565-8.
Thyroid hormone receptors (TRs) are ligand-dependent transcription factors that bind to thyroid hormone response elements (TREs) to mediate positive and negative regulation of transcription of thyroid hormone-responsive genes. TR binding to TREs can be enhanced by interaction with a nuclear protein, triiodothyronine (T3) receptor auxiliary protein (TRAP). There are two major isoforms of thyroid hormone receptors, TR alpha-1 and TR beta-1, which are encoded on two separate genes. We studied the binding of TR alpha-1 and TR beta-1 to several TREs: the chick lysozyme TRE (F2), which is positively regulated by T3; rabbit beta-myosin heavy chain TRE, which is negatively regulated by T3; and an idealized inverted palindrome, TRElap. We demonstrate the formation of homodimers, TR alpha/TR beta dimers, and TR/TRAP heterodimers when receptor is bound to these DNA sequences. Surprisingly, we found that T3 decreased TR alpha-1 and TR beta-1 homodimer binding in a dose-dependent manner to these TREs as well as TR alpha/TR beta dimer binding to F2. In contrast, T3 did not affect TR/TRAP heterodimer binding to TREs suggesting that this heterodimer may be the stable complex occupying TREs in the presence of ligand.
甲状腺激素受体（TRs）是配体依赖性转录因子，可与甲状腺激素反应元件（TREs）结合，介导甲状腺激素反应性基因转录的正调控和负调控。TR与TREs的结合可通过与核蛋白三碘甲状腺原氨酸（T3）受体辅助蛋白（TRAP）相互作用而增强。甲状腺激素受体有两种主要的亚型，TRα-1和TRβ-1，它们由两个不同的基因编码。我们研究了TRα-1和TRβ-1与几种TREs的结合情况：鸡溶菌酶TRE（F2），受T3正调控；兔β-肌球蛋白重链TRE，受T3负调控；以及一个理想化的反向回文序列TRElap。当受体与这些DNA序列结合时，我们证明了同二聚体、TRα/TRβ二聚体和TR/TRAP异二聚体的形成。令人惊讶的是，我们发现T3以剂量依赖性方式降低了TRα-1和TRβ-1同二聚体与这些TREs的结合，以及TRα/TRβ二聚体与F2的结合。相比之下，T3不影响TR/TRAP异二聚体与TREs的结合，这表明这种异二聚体可能是在配体存在下占据TREs的稳定复合物。
