The transcription factor basic transcription element-binding protein 1 is a direct thyroid hormone response gene in the frog Xenopus laevis

The transcription factor basic transcription element-binding protein 1 is a direct thyroid hormone response gene in the frog Xenopus laevis
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DOI:
10.1210/en.2002-220126
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发表时间:
2002-09-01
期刊:
影响因子:
4.8
通讯作者:
Kanamori, A
Kanamori, A
中科院分区:
医学2区
文献类型:
--
作者:
Furlow, JD;Kanamori, A

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已经确定了几个基因,在蝌蚪组织中被甲状腺激素激活或抑制。非洲爪蟾的形态学一个快速和强烈诱导的基因编码非洲爪蟾同源物的基本转录元件结合蛋白1(xBTEB1),SP1相关的转录因子。xBTEB1具有与哺乳动物BTEB1相似的DNA结合活性和转录激活特性。甲状腺激素依赖性调节BBTEB1进行了研究,使用改良的电泳迁移率变动分析扫描基因组DNA的受体结合位点。由于四倍体X. laevis基因组中,xBTEB1是重复的,甲状腺激素调节两个拷贝。一个共识甲状腺激素反应元件(TRE)位于这两个基因的转录起始位点的上游。TRE嵌套在这两个基因之间的200 bp高度序列保守区域内,这两个基因在数百万年前复制。TRE在使用异源启动子或其天然环境的转染测定中充当强响应元件。因此,最早的甲状腺激素诱导的基因之一,在蝌蚪是一个转录因子的调节,通过进化保守的TRE。预测xBTEB1在下游基因调控中发挥重要作用,导致变态时组织的生长和重塑。
Several genes have been identified that are activated or repressed by thyroid hormone in tadpole tissues during meta. morphosis of the frog Xenopus laevis. One rapidly and strongly induced gene encodes the Xenopus homolog of basic transcription element-binding protein 1 (xBTEB1), an SP1-related transcription factor. xBTEB1 has similar DNA-binding activity and transcriptional activation properties as mammalian BTEB1. The thyroid hormone-dependent regulation of BBTEB1 was investigated using a modified electrophoretic mobility shift assay to scan genomic DNA for receptor-binding sites. Due to the tetraploid X. laevis genome, xBTEB1 is duplicated, and thyroid hormone regulates both copies. A consensus thyroid hormone response element (TRE) lies far upstream of the transcriptional start site of both genes. The TRE is nested within a 200-bp region of high sequence conservation between these two genes that duplicated millions of years ago. The TRE acts as a strong response element in transfection assays using a heterologous promoter or its native context. Thus, one of the earliest thyroid hormone-induced genes in tadpoles is a transcription factor regulated through an evolutionarily conserved TRE. xBTEB1 is predicted to play an important role in downstream gene regulation leading to the growth and remodeling of tissues at metamorphosis.