TISSUE-SPECIFIC EXPRESSION OF THE RAT AH-RECEPTOR AND ARNT MESSENGER-RNAS

TISSUE-SPECIFIC EXPRESSION OF THE RAT AH-RECEPTOR AND ARNT MESSENGER-RNAS
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DOI:
10.1093/nar/22.15.3038
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发表时间:
1994-08-11
影响因子:
14.9
通讯作者:
BRADFIELD, CA
BRADFIELD, CA
中科院分区:
生物学2区
文献类型:
--
作者:
CARVER, LA;HOGENESCH, JB;BRADFIELD, CA

文献摘要

被引文献

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Ah-receptor(AHR)是一种配体激活的转录因子,其介导激动剂如2,3,7,8-四氯二苯并-p-二恶英的生物学效应。在结合激动剂后,AHR与称为ARNT的结构相关蛋白质二聚化,然后该异源二聚体结合同源增强子元件并激活靶基因的表达。在这份报告中,我们描述了大鼠AHR cDNA和大鼠ARNT cDNA片段的克隆,用作核糖核酸酶保护分析的探针。核糖核酸酶保护分析表明,大鼠AHR mRNA在肺>胸腺>肾>肝中表达水平最高,而在心脏和脾脏中表达水平较低。大鼠AHR和ARNT mRNA在检查的8种组织中以很大程度上协调的方式表达,但胎盘除外,胎盘中AHR水平相对较低,与ARNT相比。在这些实验中,克隆了AHR的一种罕见剪接变体,其编码在配体结合结构域中具有缺失的蛋白质。体外表达研究表明,与全长AHR相反,剪接变体在ARNT存在下既不结合配体也不结合同源增强子元件。
The Ah-receptor (AHR) is a ligand activated transcription factor that mediates the biological effects of agonists such as 2,3,7,8-tetrachlorodibenzo-p-dioxin. Upon binding agonists, the AHR dimerizes with a structurally related protein known as ARNT and this heterodimer then binds cognate enhancer elements and activates the expression of target genes. In this report we describe the cloning of the rat AHR cDNA and a fragment of the rat ARNT cDNA for use as probes in ribonuclease protection analysis. Ribonuclease protection analysis indicated that the rat AHR mRNA is expressed at the highest levels in the lung > thymus > kidney > liver while lower levels were expressed in heart and spleen. The rat AHR and ARNT mRNAs were expressed in a largely coordinate manner across the eight tissues examined with the exception of the placenta where AHR levels were relatively low compared to ARNT. In these experiments, a rare splice variant of the AHR was cloned that encoded a protein with a deletion in the ligand binding domain. In vitro expression studies demonstrated that in contrast to the full length AHR, the splice variant did not bind ligand nor did it bind to a cognate enhancer element in the presence of ARNT.