Two uniquely arranged thyroid hormone response elements in the far upstream 5' flanking region confer direct thyroid hormone regulation to the murine cholesterol 7alpha hydroxylase gene.
Two uniquely arranged thyroid hormone response elements in the far upstream 5' flanking region confer direct thyroid hormone regulation to the murine cholesterol 7alpha hydroxylase gene.
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在遥远的5'侧面区域中，两个独特布置的甲状腺激素反应元件将直接的甲状腺激素调节与鼠胆固醇7alpha羟化酶基因调节。
DOI：
10.1093/nar/gkl506
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发表时间：
2006
影响因子：
14.9
通讯作者：
Osborne TF
中科院分区：
文献类型：
--
作者：
Shin DJ;Plateroti M;Samarut J;Osborne TF
胆固醇7α羟化酶（CYP 7A 1）是胆固醇转化为胆汁酸的关键酶，其活性对维持适当的胆固醇水平至关重要。小鼠CYP 7A 1基因在体内可被甲状腺激素高度诱导，并且甲状腺激素和血清胆固醇之间存在负相关关系。尽管基因表达已被证明是上调，是否诱导介导的直接作用的甲状腺激素对CYP 7A 1启动子从未建立。使用基因靶向小鼠，我们表明，两种TR亚型中的任何一种都足以维持正常的肝脏CYP 7A 1表达，但两者的缺失导致表达显著降低。我们还在CYP 7A 1 5′侧翼序列中发现了两个新的功能性甲状腺激素受体结合位点，位于转录起始位点上游3 kb处。一个位点是DR-0，这是一种不寻常类型的TR反应元件，另一个位点仅由TR/类维生素A X受体（RXR）结合所需的单个可识别的半位点组成。这两个独立的TR结合位点间隔很近，都是甲状腺激素完全诱导CYP 7A 1启动子所必需的，尽管DR-0位点更关键。
Cholesterol 7α hydroxlyase (CYP7A1) is a key enzyme in cholesterol catabolism to bile acids and its activity is important for maintaining appropriate cholesterol levels. The murine CYP7A1 gene is highly inducible by thyroid hormone in vivo and there is an inverse relationship between thyroid hormone and serum cholesterol. Eventhough gene expression has been shown to be upregulated, whether the induction was mediated through a direct effect of thyroid hormone on the CYP7A1 promoter has never been established. Using gene targeted mice, we show that either of the two TR isoforms are sufficient to maintain normal hepatic CYP7A1 expression but a loss of both results in a significant decrease in expression. We also identified two new functional thyroid hormone receptor-binding sites in the CYP7A1 5′ flanking sequence located 3 kb upstream from the transcription start site. One site is a DR-0, which is an unusual type of TR response element, and the other consists of only a single recognizable half site that is required for TR/retinoid X receptor (RXR) binding. These two independent TR-binding sites are closely spaced and both are required for full induction of the CYP7A1 promoter by thyroid hormone, although the DR-0 site was more crucial.
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影响因子：
--
作者：
FORMAN, BM;CASANOVA, J;SAMUELS, HH
通讯作者：
SAMUELS, HH
影响因子：
64.8
作者：
KLIEWER, SA;UMESONO, K;EVANS, RM
通讯作者：
EVANS, RM
影响因子：
--
作者：
Gullberg, H;Rudling, M;Vennström, B
通讯作者：
Vennström, B
DOI：
10.1006/bbrc.1999.0980
发表时间：
1999-07-14
影响因子：
3.1
作者：
Chen, J;Cooper, AD;Levy-Wilson, B
通讯作者：
Levy-Wilson, B
影响因子：
4.8
作者：
Hashimoto, K;Cohen, RN;Wondisford, FE
通讯作者：
Wondisford, FE