IDENTIFICATION OF A NEW SUBCLASS OF ALU DNA REPEATS WHICH CAN FUNCTION AS ESTROGEN RECEPTOR-DEPENDENT TRANSCRIPTIONAL ENHANCERS
IDENTIFICATION OF A NEW SUBCLASS OF ALU DNA REPEATS WHICH CAN FUNCTION AS ESTROGEN RECEPTOR-DEPENDENT TRANSCRIPTIONAL ENHANCERS
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DOI：
10.1074/jbc.270.39.22777
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发表时间：
1995-09-29
影响因子：
4.8
通讯作者：
MCDONNELL, DP
中科院分区：
文献类型：
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作者：
NORRIS, J;FAN, DJ;MCDONNELL, DP
我们利用酵母中的遗传选择系统来鉴定人类基因组内新的雌激素反应性基因，并定义负责其雌激素反应性的 BRCA-1 基因中的序列。这种方法导致在 DNA 重复的 Alu 家族中鉴定出一个新的亚类，该亚类与已知的 Alu 序列不同，并获得了作为雌激素受体依赖性增强子发挥作用的能力。重要的是，这些新元件赋予受体依赖性雌激素反应性当在哺乳动物细胞中进行测定时，这种转录活性可以通过添加三种不同类别的雌激素受体拮抗剂中的任一种来减弱，这表明这些元件充当经典的雌激素受体依赖性增强子。此外，这种增强子活性仅限于DNA重复的特定子集，因为四个主要亚家族的共有Alu元件不响应雌激素受体。以前，大多数 Alu 序列被认为是功能惰性的，然而，这项工作提供了强有力的证据，表明一个重要的子集可以赋予它们所在的启动子雌激素反应性。显然，Alu 序列现在必须被认为是在含有雌激素受体的细胞中调节基因转录的重要贡献者。
We have utilized a genetic selection system in yeast to identify novel estrogen-responsive genes within the hu man genome and to define the sequences in the BRCA-1 gene responsible for its estrogen responsiveness, This approach led to the identification of a new subclass within the Alu family of DNA repeats which have diverged from known Alu sequences and have acquired the ability to function as estrogen receptor-dependent enhancers, Importantly, these new elements confer receptor-dependent estrogen responsiveness to a heterologous promoter when assayed in mammalian cells, This transcriptional activity can be attenuated by the addition of either of three different classes of estrogen receptor antagonists, indicating that these elements function as classical estrogen receptor-dependent enhancers, Furthermore, this enhancer activity is restricted to a specific subset of DNA repeats because consensus Alu elements of four major subfamilies do not respond to the estrogen receptor. Previously, most Alu sequences have been considered to be functionally inert, However, this work provides strong evidence that a significant subset can confer estrogen responsiveness upon a promoter within which they are located, Clearly, Alu sequences must now be considered as important contributors to the regulation of gene transcription in estrogen receptor-containing cells.