Hallenbeck P L, Phyillaier M, Nikodem V M
Genetics and Biochemistry Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892.
J Biol Chem. 1993 Feb 25;268(6):3825-8.
The thyroid hormone (TH)-inducible expression of some genes has recently been shown to be enhanced by 9-cis-retinoic acid (9-cis-RA) receptor (RXR). This effect appears to be at least partially elicited by the ability of RXR to heterodimerize with TH receptor (THR) and enhance its binding to the cis-acting thyroid hormone responsive elements (TREs) found within those genes. However, whether RXR beta enhances TH/THR-mediated transactivation of all Tre-containing genes, and if RXR has any effect on TH-dependent negative regulation are not known. In the present study, we show that the TH/THR-inducible expression of the myelin basic protein (MBP) gene is not enhanced by RXR beta, despite high affinity binding of the RXR beta.THR alpha heterodimer to the MBP-TRE. We also demonstrate that RXR beta reverses the TH/THR-dependent down-regulation mediated by the negative TRE found within the promoter of the mouse thyroid stimulating hormone gene (TSH). The ligand for RXR beta (9-cis-RA), either alone or in combination with TH, did not enhance the transcription mediated by either the MBP-TRE, TSH-TRE, or the malic enzyme (ME)-TRE. However, the ME-TRE is known to confer RXR beta-dependent enhancement of TH-induced gene expression. Thus, the capacity of RXR beta to modulate TH-dependent transcriptional regulation depends upon the nature of the TRE.
最近研究表明，甲状腺激素（TH）诱导的某些基因表达可被9-顺式视黄酸（9-cis-RA）受体（RXR）增强。这种效应似乎至少部分是由RXR与甲状腺激素受体（THR）形成异源二聚体并增强其与这些基因中顺式作用甲状腺激素反应元件（TREs）结合的能力所引发的。然而，RXRβ是否能增强TH/THR介导的所有含TRE基因的反式激活，以及RXR对TH依赖性负调控是否有任何影响尚不清楚。在本研究中，我们发现尽管RXRβ.THRα异源二聚体与髓磷脂碱性蛋白（MBP）-TRE具有高亲和力结合，但RXRβ并不能增强MBP基因的TH/THR诱导表达。我们还证明，RXRβ可逆转由小鼠促甲状腺激素基因（TSH）启动子内的负性TRE介导的TH/THR依赖性下调。RXRβ的配体（9-顺式视黄酸）单独或与TH联合使用时，均不能增强由MBP-TRE、TSH-TRE或苹果酸酶（ME）-TRE介导的转录。然而，已知ME-TRE可赋予RXRβ依赖性增强TH诱导的基因表达。因此，RXRβ调节TH依赖性转录调控的能力取决于TRE的性质。
