GENE STRUCTURE AND REGULATION OF N-NITROSODIMETHYLAMINE DEMETHYLASE

N-亚硝基二甲胺脱甲基酶的基因结构和调控

• 批准号: 3916875
• 负责人: F J GONZALEZ
• 金额: --
• 依托单位: DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3916875
• 关键词: DNA methylation; chemical carcinogenesis; cytochrome P450; developmental genetics; diabetes mellitus; enzyme induction /repression; ethanol; genetic mapping; genetic transcription; human tissue; liver metabolism; messenger RNA; methylation; nitrosamines; nucleic acid probes; nucleic acid sequence; toxin metabolism

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.

参与代谢和活化的主要酶 小亚硝胺化合物是乙醇诱导的 P450IIIEI。 这种酶是由乙醇、禁食和糖尿病通过 转录后机制。 IIIEI基因变成 出生后不久转录激活。 研究 IIIEI 基因、大鼠和人类基因组的调控 分离克隆并对其进行完整测序。 两个基因 P450II基因中含有9个与其他基因相似的外显子 家庭。 两个基因之间显着的核苷酸相似性是 在基因的 150 bp 内检测到。 启动子区域 能够驱动荧光素酶基因的转录 转染至大鼠肝癌细胞。 IIEI 被本地化为 小鼠 7 号染色体和人类 10 号染色体利用体细胞 细胞杂交作图策略。 胞嘧啶的分析 IIIEI 基因的甲基化状态揭示了上游位点 大鼠 IIIEI 转录起始位点去甲基化 与转录激活后24小时内一致 出生。 IIEI 基因的甲基化变化也被检测到 人类在发展过程中。 A标签I限制性片段长度 利用 IIEI 检测人类 IIIEI 基因的多态性 cDNA probe.