Dioxin-responsive AHRE-II gene battery: identification by phylogenetic footprinting
Dioxin-responsive AHRE-II gene battery: identification by phylogenetic footprinting
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DOI：
10.1016/j.bbrc.2004.06.177
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发表时间：
2004-08-27
影响因子：
3.1
通讯作者：
Okey, AB
中科院分区：
文献类型：
--
作者：
Boutros, PC;Moffat, ID;Okey, AB
我们通过最近发现的 AHRE-II（“XRE-II”）增强子元件鉴定了一组对二恶英做出反应的基因。通过全基因组转录因子结合位点搜索和系统发育足迹，总共鉴定了 36 个含有 AHRE-II 基序的基因，这些基序在人类、小鼠和大鼠基因直向同源物中保守。对接受 213.7,8-四氯二苯并-对二恶英处理的大鼠肝脏进行的微阵列实验显示，3 小时后，这 36 个基因中的 13 个基因的 mRNA 水平发生了统计学上的显着变化，19 小时后，15 个基因的 mRNA 水平发生了统计学上的显着变化。通过本体分析对这组响应基因进行了功能表征，发现其富含离子通道和转运蛋白。我们对 36 个假定的 AHRE-II 调节基因的鉴定突出了芳烃受体 (AHR) 的调节多功能性以及 AHR 及其二聚化伙伴 ARNT 既充当配体激活转录因子（在 AHRE-I 上）又充当配体激活共激活子（在 AHRE-II 上）的能力。总的来说，这些结果表明 AHRE-II 诱导机制由多个基因采用，并提供了配体激活共激活剂基因组的第一个分类。 (C) 2004 Elsevier Inc. 保留所有权利。
We identified a set of genes that respond to dioxins through the recently discovered AHRE-II ("XRE-II") enhancer element. A total of 36 genes containing AHRE-II motifs conserved across human, mouse, and rat gene orthologs were identified by genome-wide transcription-factor binding-site searches and phylogenetic footprinting. Microarray experiments on liver from rats treated with 213.7,8-tetrachlorodibenzo-p-dioxin revealed statistically significant changes in mRNA levels for 13 of these 36 genes after three hours and 15 genes after 19h. The set of responsive genes was functionally characterized by ontological analysis and found to be enriched in ion-channels and transporters. Our identification of 36 putatively AHRE-II-regulated genes highlights the regulatory versatility of the aryl hydrocarbon receptor (AHR) and the ability of the AHR and its dimerization partner, ARNT, to act both as a ligand-activated transcription-factor (on AHRE-I) and as a ligand-activated coactivator (on AHRE-II). Collectively, these results demonstrate that the AHRE-II induction mechanism is employed by multiple genes and provide the first categorization of the gene battery of a ligand-activated coactivator. (C) 2004 Elsevier Inc. All rights reserved.