TR4 orphan receptor represses the human steroid 21-hydroxylase gene expression through the monomeric AGGTCA motif.
TR4 orphan receptor represses the human steroid 21-hydroxylase gene expression through the monomeric AGGTCA motif.
复制标题
TR4 孤儿受体通过单体 AGGTCA 基序抑制人类固醇 21-羟化酶基因表达。
DOI：
10.1006/bbrc.2001.5342
复制
发表时间：
2001
影响因子：
3.1
通讯作者：
Chang,C
中科院分区：
文献类型：
--
作者：
Lee,HJ;Lee,YF;Chang,C
人类TR 4孤儿受体（TR 4）是核受体超家族的成员。它作为一种转录因子，调节和控制许多重要的生理功能。已经证明TR 4可以作为同源二聚体结合到含有AGGTCA共有基序的两个直接重复的DNA应答元件。令人惊讶的是，我们的数据显示，人类类固醇21-羟化酶（21-OHase）基因的表达可以被TR 4通过其5′侧翼区（核苷酸编号1431-1444，5′-GGAAAAAGGTCAGG-3′）的单体AGGTCA基序（− 228 TR 4 RE）抑制。电泳迁移率变动分析显示TR 4和单体− 288 TR 4 RE基序之间特异性结合，解离常数为0.4 nM。然而，TR 4不与类视黄醇X受体α或SHP（短异二聚体伴侣）孤儿受体形成异二聚体。此外，双荧光素酶和氯霉素乙酰转移酶试验都证明TR 4可以通过21-OHase基因的− 228 TR 4 RE作为阻遏物发挥作用。总之，我们的数据表明，TR 4可能结合到一个单体的DNA反应元件，并在抑制21-OHase基因的表达发挥重要作用。
The human TR4 orphan receptor (TR4) is a member of the nuclear receptor superfamily. It functions as a transcriptional factor which regulates and controls many important physiological functions. It has been documented that TR4 may bind as a homodimer to a DNA response element containing two direct repeats of the AGGTCA consensus motif. Surprisingly, our data reveal that the expression of the human steroid 21-hydroxylase (21-OHase) gene could be repressed by TR4 via the monomeric AGGTCA motif (−228TR4RE) at its 5′ flanking region (nucleotide numbers 1431–1444, 5′-GGAAAAAGGTCAGG-3′). Electrophoretic mobility shift assay showed specific binding with a dissociation constant of 0.4 nM between TR4 and the monomeric −288TR4RE motif. However, TR4 does not form heterodimers with either retinoid X receptor alpha or SHP (short heterodimer partner) orphan receptor. Additionally, both dual-luciferase and chloramphenicol acetyltransferase assays demonstrated that TR4 can function as a repressor via the −228TR4RE of the 21-OHase gene. In conclusion, our data suggest that TR4 may bind to a monomeric DNA response element and play an important role in the suppression of the 21-OHase gene expression.