ARNT gene multiplicity in amphibians: characterization of ARNT2 from the frog Xenopus laevis.
ARNT gene multiplicity in amphibians: characterization of ARNT2 from the frog Xenopus laevis.
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DOI：
10.1002/jez.b.45
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发表时间：
2003-12
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影响因子：
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通讯作者：
A. J. Rowatt;John J. DePowell;W. Powell
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作者：
A. J. Rowatt;John J. DePowell;W. Powell
芳香烃受体核转运子（ARNT）是Per-ARNT-Sim（PAS）蛋白超家族的成员，其是介导细胞对各种发育信号和环境条件的反应的转录因子。作为一种β类（“伴侣”）PAS蛋白，ARNT表现出与几种α类（“传感器”）蛋白形成转录活性异二聚体的能力，所述α类蛋白包括芳烃受体（AHR）、缺氧诱导因子（HIF）和单一思维（Sim）蛋白。哺乳动物中有两种基因编码不同形式的ARNT：ARNT 1广泛表达，ARNT 2仅限于成人的大脑和肾脏以及胚胎的特定神经和鳃组织。相比之下，鱼显然只表达一个ARNT基因，尽管在不同的物种中，这可能是ARNT 1或ARNT 2。为了了解ARNT蛋白在整个脊椎动物谱系中的进化，我们从两栖动物非洲爪蟾的早期生命阶段分离出了ARNT cDNA。所编码的蛋白质结合与小鼠AHR一致的同源DNA序列。系统发育分析表明，该序列与哺乳动物ARNT 2同源，与最近报道的X.平滑ARNT 1. ARNT 2 mRNA的表达开始晚于ARNT 1（第22阶段与第8阶段），表明这两种蛋白质在发育过程中发挥不同的作用。因此，在两个具有不同表达模式的高度保守的ARNT旁系同源物的表达中，X. leevis类似哺乳动物而不是鱼。PAS蛋白（包括ARNT）的数量和功能多样性可能是发育编程和对环境条件的生化反应存在显著物种差异的基础。多种两栖类ARNT旁系同源物的鉴定是了解ARNT在脊椎动物中进化和功能变异的重要一步。
The aryl hydrocarbon receptor nuclear translocator (ARNT) is a member of the Per-ARNT-Sim (PAS) protein superfamily, transcription factors that mediate the cellular responses to various developmental signals and environmental conditions. A beta-class ("partner") PAS protein, ARNT exhibits the capacity to form transcriptionally active heterodimers with several alpha-class ("sensor") proteins, including the aryl hydrocarbon receptors (AHRs), the hypoxia-inducible factors (HIFs), and the Single minded (Sim) proteins. Two genes encode different forms of ARNT in mammals: ARNT1, which is widely expressed, and ARNT2, which is limited to the brain and kidneys of adults and specific neural and branchial tissues of embryos. In contrast, fish apparently express only a single ARNT gene, although in different species, this may be either ARNT1 or ARNT2. In efforts to understand the evolution of ARNT proteins throughout the vertebrate lineage, we isolated an ARNT cDNA from early life stages of the amphibian Xenopus laevis. The encoded protein binds cognate DNA sequences in concert with mouse AHR. Phylogenetic analysis reveals that this sequence is orthologous to mammalian ARNT2 and paralogous to the recently reported X. laevis ARNT1. ARNT2 mRNA expression begins later than ARNT1 (stage 22 vs. stage 8), suggesting the two proteins play distinct roles during development. Hence, in the expression of two well-conserved ARNT paralogs with distinct expression patterns, X. laevis resembles mammals rather than fish. Diversity in the number and function of PAS proteins, including ARNT, may underlie significant species differences in developmental programming and biochemical response to environmental conditions. The identification of multiple amphibian ARNT paralogs represents an important step in the understanding of evolution and functional variation of ARNT in vertebrates.