GENE STRUCTURE AND REGULATION OF N-NITROSODIMETHYLAMINE DEMETHYLASE

参与代谢和激活的主要酶 小的亚硝胺化合物是乙醇诱导的P450 IIEI。 这种酶是由乙醇诱导，禁食和糖尿病通过一个 转录后机制 IIEI基因成为 在出生后不久就被转录激活。 为了研究IIEI基因的调控， 分离克隆并完全测序。 两个基因 含有9个与P450II基因中其他基因相似的外显子 家人 两个基因之间的显著核苷酸相似性是 在基因衣壳的150 bp内检测到。 启动子区 能够驱动荧光素酶基因的转录， 转染大鼠肝癌细胞。 IIEI被定位为 小鼠7号染色体和人10号染色体的染色体组学研究 细胞杂交作图策略。 胞嘧啶分析 IIEI基因的甲基化状态显示， 的大鼠IIEI转录起始位点被去甲基化 在24小时内与转录激活同时发生， 出生 IIEI基因的甲基化变化也在100例正常人中检测到。 人类在发展过程中 A标签I限制性片段长度 利用IIEI检测人IIEI基因的多态性 cDNA探针。

The principal enzyme involved in the metabolism and activation of small nitrosamine compounds is the ethanol-inducible P450IIEI. This enzyme is induced by ethanol, fasting and diabetes through a post-transcriptional mechanism. The IIEI gene becomes transcriptionally activated soon after birth. To study the regulation of the IIEI gene, rat and human genomic clones were isolated and completely sequenced. Both genes contained nine exons similar to other genes in the P450II gene family. Significant nucleotide similarity between both genes was detected within 150 bp of the genes'capsite. The promoter regions were able to drive transcription of the luciferase gene when transfected into rat hepatoma cells. The IIEI was localized to mouse chromosome 7 and human chromosome 10 by use of the somatic cell hybrids mapping strategy. Analysis of the cytosine methylation status of the IIEI gene revealed that sites upstream of the rat IIEI transcription start site are demethylated coincident with transcriptional activation within 24 hours after birth. Methylation changes in the IIEI gene were also detected in humans during development. A Tag I restriction fragment length polymorphism was detected in the human IIEI gene by use of the IIEI cDNA probe.