REGULATORY ELEMENTS CONTROLLING THE BASAL AND DRUG-INDUCIBLE EXPRESSION OF GLUTATHIONE S-TRANSFERASE YA SUBUNIT GENE
REGULATORY ELEMENTS CONTROLLING THE BASAL AND DRUG-INDUCIBLE EXPRESSION OF GLUTATHIONE S-TRANSFERASE YA SUBUNIT GENE
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DOI：
10.1089/dna.1.1989.8.399
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发表时间：
1989-07-01
期刊：
影响因子：
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通讯作者：
BENSIMON, A
中科院分区：
文献类型：
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作者：
DANIEL, V;SHARON, R;BENSIMON, A
谷胱甘肽S-转移酶Ya亚单位的合成在哺乳动物肝脏中由化学物质如苯巴比妥和3-甲基胆蒽诱导。为了研究这种诱导的机制，将小鼠谷胱甘肽S-转移酶Ya亚基基因的5“-侧翼区与氯霉素乙酰转移酶的结构基因融合。将该融合基因导入肝癌细胞，检测表达的乙酰转移酶活性。在Ya基因的5“-侧翼区域中鉴定了至少两个顺式调节元件：一个负责基础表达水平，存在于序列中高达~ 0.2kb;另一个负责通过芳香族化合物如β-葡萄糖诱导表达。在-0.2kb ~-1.6kb的序列中，诱导元件仅在具有正常芳香族化合物受体的细胞中起作用，并且它保留对β-受体的应答性。当转染到同源（小鼠）或异源（大鼠，人）肝癌细胞中时，一个150 bp的区域上游的小鼠Ya基因的转录起始位点进行了研究的顺式作用转录元件，被识别的特定的DNA结合蛋白。我们表明，通过DNA酶I足迹分析，使用提取物从肝细胞核的Ya基因启动子包含，除了TATA和CCAAT盒，一个更远的元素，结合一种蛋白质，这可能是相关的核因子1（NF 1）的家庭。
The synthesis of the glutathione S-transferse Ya subunit is induced in the mammalian liver by chemicals such as phenobarbital and 3-methylcholanthrene. To study the mechanism of this induction, the 5''-flanking region of a mouse glutathione S-transferase Ya subunit gene was fused to the structural gene for chloramphenicol acetyltransferase. The fusion gene was introduced into hepatoma cells for the assay of the expressed acetyltransferase activity. At least two cis-regulatory elements were identified in the 5''-flanking region of the Ya gene: one, responsible for the basal level of expression, is present in the sequence up to -0.2 kb; another, responsible for the inducible expression by aromatic compounds such as .beta.-naphthoflavone and 3-methylcholanthrene, is located in the sequence from -0.2 kb to -1.6 kb. The inducible element was functional only in cells with normal aromatic compound receptors, and it retained responsiveness to .beta.-naphthoflavone when transfected into homologous (mouse) or heterologous (rat, human) hepatoma cells. A 150-bp region upstream from the transcription initiation site of the mouse Ya gene was investigated for cis-acting transcriptional elements that are recognized by specific DNA-binding proteins. We show by DNase I foot-printing assays using extracts from liver nuclei that the Ya gene promoter contains, in addition to the TATA and CCAAT boxes, a more distal element that binds a protein which is probably related to the family of nuclear factor 1 (NF1).