Schmidt J V, Carver L A, Bradfield C A
Department of Pharmacology, Northwestern University Medical School, Chicago, Illinois 60611.
J Biol Chem. 1993 Oct 15;268(29):22203-9.
The AH receptor is a ligand-activated transcription factor that mediates the biological effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin. The AH receptor has primary sequence homology to its dimerization partner the AH receptor nuclear translocator, and to the Drosophila proteins Sim and Per. Characterization of the gene encoding the murine AH receptor (Ahr gene) reveals that its structural organization is also conserved with respect to the sim gene, since 6 of 11 Ahr exons are spliced at homologous sites. Interestingly, little splicing homology was observed between the Ahr and per genes. The promoter of the Ahr gene is GC-rich and contains no TATA or CCAAT boxes; however, sequence analysis has shown several binding sites for the transcription factor Sp1 (GC boxes). Additionally we have identified a potential cAMP response element, AP-1 and E box sites, and two elements demonstrated in other genes to confer placenta-specific expression. Using a restriction fragment length polymorphism in exon 7 and recombinant inbred mouse lines, the Ahr gene was found to be concordant with the phenotypically defined Ahr locus, supporting the identity of these two genetic elements.
芳烃受体是一种配体激活的转录因子,可介导2,3,7,8-四氯二苯并对二恶英的生物学效应。芳烃受体与其二聚化伴侣芳烃受体核转运蛋白以及果蝇蛋白Sim和Per具有一级序列同源性。对编码小鼠芳烃受体的基因(Ahr基因)的表征表明,其结构组织在sim基因方面也具有保守性,因为11个Ahr外显子中有6个在同源位点进行剪接。有趣的是,在Ahr和per基因之间几乎没有观察到剪接同源性。Ahr基因的启动子富含GC,且不包含TATA或CCAAT框;然而,序列分析显示了转录因子Sp1的几个结合位点(GC框)。此外,我们还鉴定出一个潜在的cAMP反应元件、AP-1和E框位点,以及在其他基因中显示可赋予胎盘特异性表达的两个元件。利用外显子7中的限制性片段长度多态性和重组近交系小鼠,发现Ahr基因与表型定义的Ahr位点一致,支持这两个遗传元件的同一性。