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首页> 外文期刊>Molecular and Cellular Biology >A novel, cell-type-specific mechanism for estrogen receptor-mediated gene activation in the absence of an estrogen-responsive element.
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A novel, cell-type-specific mechanism for estrogen receptor-mediated gene activation in the absence of an estrogen-responsive element.

机译：在没有雌激素响应元件的情况下，一种新型的细胞类型特异性机制，用于雌激素受体介导的基因激活。

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The estrogen receptor (ER) typically activates gene transcription by binding to estrogen-responsive elements (EREs). The brain creatine kinase (BCK) promoter is responsive to estrogen but contains no ERE-related sequence. To investigate the mechanism of estrogen induction, we have introduced the estrogen receptor into HeLa cells and primary rat cardiomyocytes and fibroblasts along with 195 bp of BCK promoter linked to a chloramphenicol acetyltransferase (CAT) reporter gene. A 10-fold stimulation of CAT activity was observed in the presence of beta-estradiol in both HeLa and rat primary fibroblasts, but no induction was observed in primary rat cardiomyocytes. In contrast, a control vitellogenin gene construct which contains a typical ERE was induced in an ER-dependent manner in all cell types studied. Estrogen induction in HeLa was not sensitive to cycloheximide and was blocked by the ER antagonists tamoxifen and ICI 164,384. Analysis of 5' deletion and linker-scanning mutations indicates sequences between bp -45 and -75 including a TA-rich sequence and a CCAAT sequence to be crucial for stimulation of the BCK promoter by the ER. BCK estrogen induction is dependent on the DNA-binding domain and transactivation domain TAF2 of the ER. However, direct DNA binding is probably not required. Taken together, these results suggest a novel mechanism for ER-mediated gene activation. This mechanism is consensus ERE independent and cell type specific and requires interactions between the ER and molecules capable of interacting with the BCK promoter TA-rich region.
机译：雌激素受体（ER）通常通过与雌激素反应元件（ERE）结合来激活基因转录。脑肌酸激酶（BCK）启动子对雌激素有反应，但不包含ERE相关序列。为了研究雌激素诱导的机制，我们将雌激素受体与195 bp的氯霉素乙酰转移酶（CAT）报告基因连接的BCK启动子一起引入了HeLa细胞，原代大鼠心肌细胞和成纤维细胞。在HeLa和大鼠原代成纤维细胞中都存在β-雌二醇的情况下，CAT活性提高了10倍，但在大鼠原代心肌细胞中未观察到诱导作用。相反，在所有研究的细胞类型中，以ER-依赖性方式诱导了包含典型ERE的对照卵黄蛋白原基因构建体。 HeLa中的雌激素诱导对环己酰亚胺不敏感，并被ER拮抗剂他莫昔芬和ICI 164,384阻断。对5'缺失和接头扫描突变的分析表明，在bp -45和-75之间的序列，包括富含TA的序列和CCAAT序列，对于ER刺激BCK启动子至关重要。 BCK雌激素诱导取决于ER的DNA结合结构域和反式激活结构域TAF2。但是，可能不需要直接DNA结合。两者合计，这些结果表明ER介导的基因激活的新机制。该机制是普遍的ERE独立的且是细胞类型特异性的，并且需要ER与能够与富含BCK启动子TA的区域相互作用的分子之间的相互作用。

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