Molecular characterization of the murine Ahr gene. Organization, promoter analysis, and chromosomal assignment.

Molecular characterization of the murine Ahr gene. Organization, promoter analysis, and chromosomal assignment.
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发表时间:
1993-10
期刊:
The Journal of biological chemistry
影响因子:
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通讯作者:
J. Schmidt;L. A. Carver;C. Bradfield
J. Schmidt;L. A. Carver;C. Bradfield
中科院分区:
其他
文献类型:
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作者:
J. Schmidt;L. A. Carver;C. Bradfield

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AH 受体是一种配体激活的转录因子,介导 2,3,7,8-四氯二苯并-对二恶英的生物效应。 AH 受体与其二聚化伙伴 AH 受体核易位蛋白以及果蝇蛋白 Sim 和 Per 具有主要序列同源性。编码鼠 AH 受体(Ahr 基因)的基因的表征表明,其结构组织相对于 sim 基因也是保守的,因为 11 个 Ahr 外显子中有 6 个在同源位点剪接。有趣的是,在 Ahr 和 per 基因之间观察到很少的剪接同源性。 Ahr基因的启动子富含GC,不含TATA或CCAAT盒;然而,序列分析显示了转录因子 Sp1(GC 盒)的几个结合位点。此外,我们还鉴定了潜在的 cAMP 反应元件、AP-1 和 E 盒位点,以及在其他基因中证明可赋予胎盘特异性表达的两个元件。使用外显子 7 和重组近交小鼠系中的限制性片段长度多态性,发现 Ahr 基因与表型定义的 Ahr 基因座一致,支持这两个遗传元件的同一性。
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.