Rushmore T H, King R G, Paulson K E, Pickett C B
Merck Frosst Centre for Therapeutic Research, Pointe-Claire-Dorval, PQ, Canada.
Proc Natl Acad Sci U S A. 1990 May;87(10):3826-30. doi: 10.1073/pnas.87.10.3826.
We have identified a region in the 5' flanking sequence of the 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-methyl-cholanthrene. 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.
我们已在谷胱甘肽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'侧翼序列中鉴定出一个区域，该区域包含一个独特的外源性化合物反应元件（XRE）。调控区域跨越5'侧翼序列的核苷酸-722至-682，负责Ya亚基基因部分基础水平的表达以及由平面芳香族化合物如β-萘黄酮（β-NF）和3-甲基胆蒽诱导的表达。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。除了包含β-NF反应元件的区域外，还鉴定出了Ya亚基基因的另外两个调控区域。一个区域跨越核苷酸-867至-857，其DNA序列与在几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。第二个区域跨越核苷酸-908至-899，包含一个与细胞色素P-450 IA1基因中发现的XRE相同的DNA序列。XRE序列也有助于Ya亚基基因对平面芳香族化合物的部分反应性。我们的数据表明，平面芳香族化合物对基因表达的调控可由与XRE序列不同的DNA序列介导。
