Dual oxidase 2 bidirectional promoter polymorphisms confer differential immune responses in airway epithelia.
Dual oxidase 2 bidirectional promoter polymorphisms confer differential immune responses in airway epithelia.
复制标题
双氧化酶 2 双向启动子多态性赋予气道上皮细胞不同的免疫反应。
DOI：
10.1165/rcmb.2012-0037oc
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发表时间：
2012
影响因子：
6.4
通讯作者：
Harper,RichartW
中科院分区：
文献类型：
--
作者：
Xu,Changhong;Linderholm,Angela;Grasberger,Helmut;Harper,RichartW
双氧化酶DUOX定位于呼吸道上皮细胞，是宿主抵抗细菌和病毒的重要组成部分。然而，对DUOX转录的调控知之甚少。为了更好地了解DUOX2介导的呼吸道上皮细胞抗病毒宿主防御机制，我们设计了一个双向启动子荧光素酶报告系统来识别人DUOX2/DUOXA2启动子中重要的顺式调控区域。在这份报告中，我们证明了DUOX2和DUOXA2翻译起始点之间的基因组区域在人类呼吸道组织中起着双向启动子的作用。我们还确定了DUOX2/DUOXA2启动子上双向和单向转录活性所必需的关键调控区域。重要的是，我们在启动子中发现了两个功能上重要的单核苷酸多态(SNPs)，它们对外源双链DNA的转录起着不同的调节作用。其中一个SNP，rs269855(在非洲人后裔中丰富)，赋予了最高水平的DUOX2启动子活性。携带该基因多态的个体的临床后遗症仍有待确定。
The dual oxidase enzymes, DUOX, localized to the respiratory tract epithelium, are important components of innate host defense against bacteria and virus. However, little is known regarding the regulation ofDUOXtranscription. To better understand DUOX2-mediated mechanisms of antiviral host defense in the airway epithelium, we designed a bidirectional promoter luciferase reporter system to identify important cis-regulatory regions in the humanDUOX2/DUOXA2promoter. In this report, we demonstrate that the genomic region between the translation start sites of DUOX2 and DUOXA2 functions as a bidirectional promoter in human airway tissue. We also identified key regulatory regions on theDUOX2/DUOXA2promoter that were necessary for both bidirectional and unidirectional transcriptional activity. Importantly, we discovered two functionally important single-nucleotide polymorphisms (SNPs) within the promoter that differentially regulated DUOX2/DUOXA2 transcription in response to exogenous double-stranded DNA. One of these SNPs, rs269855 (enriched in people of African descent), conferred the highest level of DUOX2 promoter activity. The clinical sequelae for individuals who carry this polymorphism remain to be determined.