Identification of direct repeat 4 as a positive regulatory element for the human TR4 orphan receptor - A modulator for the thyroid hormone target genes
Identification of direct repeat 4 as a positive regulatory element for the human TR4 orphan receptor - A modulator for the thyroid hormone target genes
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DOI：
10.1074/jbc.272.18.12215
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发表时间：
1997-05-02
影响因子：
4.8
通讯作者：
Chang, CS
中科院分区：
文献类型：
--
作者：
Lee, YF;Pan, HJ;Chang, CS
虽然TR4孤儿受体(TR4)可以通过与直接重复1-激素反应元件(DR1-HRE)和DR2-HRE的相互作用来抑制其靶基因的表达，但我们现在报道，TR4也可以通过氯霉素乙酰转移酶实验诱导含有DR4-HRE的报告基因的转录活性。电泳迁移率改变分析和Scatchard分析表明，TR4与DR4-HRE之间有很强的结合亲和力(解离常数为2 nM)。TR4介导的诱导作用不仅存在于合成的DR4-HRE中，而且还存在于某些基因中，如大鼠α-肌球蛋白重链和含有DR4或DR4样基序的S14基因，它们被认为是甲状腺激素受体的反应元件。我们的数据还表明，这种TR4介导的基因诱导是TR4剂量和DR4序列依赖的。综上所述，我们的数据表明，DR4-HRE可能是TR4的一个正调控元件，它可能能够诱导含有这种正HRE的基因的转录活性。
While the TR4 orphan receptor (TR4) is able to repress the expression of its target genes via its interaction with the direct repeat 1-hormone response element (DR1-HRE) and DR2-HRE, we now report that TR4 can also induce the transcriptional activity of the reporter gene containing a DR4-HRE via chloramphenicol acetyltransferase assay. Electrophoretic mobility shift assay and Scatchard analysis reveal a strong binding affinity (dissociation constant = 2 nM) between TR4 and DR4-HRE. The induction mediated by TR4 was detected not only in the synthetic DR4-HRE but also in some genes, such as rat alpha-myosin heavy chain and S14 genes, containing the DR4 or DR4-like motif, which have been suggested to be the response elements for a thyroid hormone receptor. Our data also demonstrate this TR4-mediated gene induction is TR4 dose- and DR4 sequence-dependent. Together, our data suggest that DR4-HRE can be a positive regulatory element for TR4, which may be able to induce the transcriptional activity of the genes containing such positive HREs.