CHARACTERIZATION OF XENOBIOTIC RESPONSIVE ELEMENTS UPSTREAM FROM THE DRUG-METABOLIZING CYTOCHROME P-450C GENE - A SIMILARITY TO GLUCOCORTICOID REGULATORY ELEMENTS
CHARACTERIZATION OF XENOBIOTIC RESPONSIVE ELEMENTS UPSTREAM FROM THE DRUG-METABOLIZING CYTOCHROME P-450C GENE - A SIMILARITY TO GLUCOCORTICOID REGULATORY ELEMENTS
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DOI：
10.1093/nar/15.10.4179
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发表时间：
1987-05-26
影响因子：
14.9
通讯作者：
FUJIIKURIYAMA, Y
中科院分区：
文献类型：
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作者：
FUJISAWASEHARA, A;SOGAWA, K;FUJIIKURIYAMA, Y
通过基因转移方法研究了控制异生素治疗药物代谢 P-450c 基因诱导表达的 DNA 元件。将P-450c基因诱导性所必需的-844至-1140bp区域的各种切割片段置于异源SV40启动子上以测试诱导性。与凝胶阻滞测定相结合的作图研究确定了两种异生物质反应元件（XRE，XRE1，-1007 - -1021bp；XRE2，-1088 - -1092bp）的存在，由约15个核苷酸组成，表达对异生物质诱导剂的增强子活性。这两个 XRE 在 15 个核苷酸中共有 10 个，如序列 CG/CTG/CC/TTG/CTCACGCT/AA 所示，并且以相反方向排列。它们与之前提出的DRE（药物反应元件）不同（Sokawa, K. et al. Proc. Natl. Acad. Sci.83, 8044–8048(1986)），并且表达了对3-甲基胆蒽反应的强增强子活性。 XRE 显示出与糖皮质激素调节元件显着的同源性，并且显然需要假定的异生物质受体的正常功能来实现诱导增强剂活性。
The DNA element governing the inducible expression of drug-metabolizing P-450c gene by xenobiotic treatments was investigated by gene transfer methods. A variety of dissected fragments from -844 to -1140bp region which was essential for the inducibility of P-450c gene were placed on the hetero-logous SV40 promoter for testing the inducibility. Mapping studies in combination with gel retardation assay defined the presence of the two xenobiotic responsive elements(XRE, XRE1, -1007 - -1021bp; XRE2, -1088 - -1092bp) composed of about 15 nucleotides which expressed the enhancer activity in response to xenobiotic inducers. The two XREs share 10 nucleotides in common out of 15 as expressed in the sequence CG/CTG/CC/TTG/CTCACGCT/AA and are arranged in the inverse orientation. They are different from DREs(drug responsive element) proposed previously(Sogawa, K. et al. Proc. Natl. Acad. Sci.83, 8044–8048(1986)) and expressed a strong enhancer activity in response to 3-methylcholanthrene. The XRE shows a significant homology with glucocort.icoid regulatory elements and apparently needs normal functions of a putative xenobiotic receptor for the inducible enhancer activity.