REGULATION OF GLUTATHIONE S-TRANSFERASE YA SUBUNIT GENE-EXPRESSION - IDENTIFICATION OF A UNIQUE XENOBIOTIC-RESPONSIVE ELEMENT CONTROLLING INDUCIBLE EXPRESSION BY PLANAR AROMATIC-COMPOUNDS

REGULATION OF GLUTATHIONE S-TRANSFERASE YA SUBUNIT GENE-EXPRESSION - IDENTIFICATION OF A UNIQUE XENOBIOTIC-RESPONSIVE ELEMENT CONTROLLING INDUCIBLE EXPRESSION BY PLANAR AROMATIC-COMPOUNDS
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DOI:
10.1073/pnas.87.10.3826
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发表时间:
1990-05-01
影响因子:
11.1
通讯作者:
PICKETT, CB
PICKETT, CB
中科院分区:
综合性期刊1区
文献类型:
--
作者:
RUSHMORE, TH;KING, RG;PICKETT, CB

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我们已经鉴定出谷胱甘肽S-转移酶(RX:谷胱甘肽R-转移酶,EC 2.5.1.18)Ya亚基基因的5''侧翼序列中包含独特的异生素响应元件(XRE)的区域。调节区跨越5''侧翼序列的核苷酸-722至-682并且负责Ya亚基基因的部分基础水平以及平面芳香族化合物例如β-萘黄酮(β-NF)和3-甲基胆蒽的诱导表达。该区域(β-NF-反应元件)的DNA序列与细胞色素P-450 IA1基因中发现的XRE的DNA序列不同。除了含有β-NF反应元件的区域之外,Ya亚基基因的另外两个调节区域也已被鉴定。其中一个区域跨越核苷酸 -867 至 -857,并且具有与多个肝脏特异性基因中发现的肝细胞核因子 1 识别基序相同的 DNA 序列。第二个区域跨越核苷酸 -908 至 -899,并包含与细胞色素 P-450 IA1 基因中发现的 XRE 相同的 DNA 序列。 XRE 序列还有助于 Ya 亚基基因对平面芳香族化合物的部分响应。我们的数据表明,平面芳香化合物对基因表达的调节可以由不同于 XRE 序列的 DNA 序列介导。
We have identified a region in the 5'' flanking sequence of glutathione S-transferase (RX:glutathione R-transferase, EC 2.5.1.18) Ya subunit gene that contains a unique xenobiotic-responsive element (XRE). The regulatory region spans nucleotides -722 to -682 of the 5'' flanking sequence and is responsible for part of the basal level as well as inducible expression of the Ya subunit gene by planar aromatic compounds such as .beta.-naphthoflavone (.beta.-NF) and 3-methylcholanthrene. The DNA sequence of this region (.beta.-NF-responsive element) is distinct from the DNA sequence of the XRE found in the cytochrome P-450 IA1 gene. In addition to the region containing the .beta.-NF-responsive element, two other regulatory regions of the Ya subunit gene have been identified. One region spans nucleotides -867 to -857 and has a DNA sequence with identity to the hepatocyte nuclear factor 1 recognition motif found in several liver-specific genes. The second region spans nucleotides -908 to -899 and contains a DNA sequence with identity to the XRE found in the cytochrome P-450 IA1 gene. The XRE sequence also contributes to part of the responsiveness of the Ya subunit gene to planar aromatic compounds. Our data suggest that regulation of gene expression by planar aromatic compounds can be mediated by a DNA sequence that is distinct from the XRE sequence.