Thyroid hormones directly activate the expression of the human and mouse uncoupling protein-3 genes through a thyroid response element in the proximal promoter region.
Thyroid hormones directly activate the expression of the human and mouse uncoupling protein-3 genes through a thyroid response element in the proximal promoter region.
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甲状腺激素通过近端启动子区域的甲状腺反应元件直接激活人和小鼠解偶联蛋白 3 基因的表达。
DOI：
10.1042/bj20041073
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Villarroya,Francesc
中科院分区：
文献类型：
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作者：
Solanes,Gemma;Pedraza,Neus;Calvo,Verónica;Vidal-Puig,Antonio;Lowell,BradfordB;Villarroya,Francesc
骨骼肌中人UCP 3（解偶联蛋白-3）基因的转录受到与脂肪酸可用性相关的代谢信号的严格调控。然而，甲状腺状态的变化也modulateUCP 3基因的表达，虽然未知的机制。我们建立了携带完整humanUCP 3基因的转基因小鼠，以研究甲状腺激素对humanUCP 3基因表达的影响。用甲状腺激素处理humanUCP 3转基因小鼠，诱导骨骼肌中人类基因的表达。此外，瞬时转染实验表明，甲状腺激素激活人类UCP 3基因启动子的转录时，MyoD和TR（甲状腺激素受体）共转染。甲状腺激素对UCP 3基因转录的作用是通过TR与UCP 3基因启动子中含有直接重复结构的近端区域的结合来介导的。该位点的完整DNA序列是甲状腺激素反应性和TR结合所必需的。染色质免疫沉淀试验表明，TR结合这种元素在体内。鼠Ucp 3基因启动子也依赖于MyoD，并在瞬时转染实验中对甲状腺激素有反应。然而，它对甲状腺激素的敏感性远低于humanUCP 3启动子。总之，UCP 3基因的转录在体内被甲状腺激素激活，这种激活是由近端启动子区的TRE（甲状腺激素反应元件）介导的。这种调节表明UCP 3基因表达与甲状腺激素对骨骼肌线粒体功能的影响之间存在联系。
The transcription of the humanUCP3(uncoupling protein-3) gene in skeletal muscle is tightly regulated by metabolic signals related to fatty acid availability. However, changes in thyroid status also modulateUCP3gene expression, albeit by unknown mechanisms. We created transgenic mice bearing the entire humanUCP3gene to investigate the effect of thyroid hormones on humanUCP3gene expression. Treatment of humanUCP3transgenic mice with thyroid hormones induced the expression of the human gene in skeletal muscle. In addition, transient transfection experiments demonstrate that thyroid hormones activate the transcription of the humanUCP3gene promoter when MyoD and the TR (thyroid hormone receptor) were co-transfected. The action of thyroid hormones onUCP3gene transcription is mediated by the binding of the TR to a proximal region in theUCP3gene promoter that contains a direct repeat structure. An intact DNA sequence of this site is required for thyroid hormone responsiveness and TR binding. Chromatin immunoprecipitation assays revealed that the TR binds this elementin vivo. The murineUcp3gene promoter was also dependent on MyoD and responsive to thyroid hormone in transient transfection assays. However, it was much less sensitive to thyroid hormone than the humanUCP3promoter. In summary,UCP3gene transcription is activated by thyroid hormone treatmentin vivo, and this activation is mediated by a TRE (thyroid hormone response element) in the proximal promoter region. Such regulation suggests a link betweenUCP3gene expression and the effects of thyroid hormone on mitochondrial function in skeletal muscle.