A role for basic transcription element-binding protein 1 (BTEB1) in the autoinduction of thyroid hormone receptor β
A role for basic transcription element-binding protein 1 (BTEB1) in the autoinduction of thyroid hormone receptor β
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DOI：
10.1074/jbc.m709306200
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发表时间：
2008-01-25
影响因子：
4.8
通讯作者：
Denver, Robert J.
中科院分区：
文献类型：
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作者：
Bagamasbad, Pia;Howdeshell, Kembra L.;Denver, Robert J.
甲状腺激素（T-3）诱导蝌蚪变态所必需的基因调控程序。对T3的最早反应是T3受体β（TR β;自诱导）和BTEB 1（基本转录元件结合蛋白1）的上调。BTEB 1是Kruppel转录因子家族的成员，与基因启动子中富含GC的区域结合。非洲爪蟾Tr β A基因的近端启动子有7个富含GC的序列，这使我们假设BTEB 1结合并调节Tr β A。在蝌蚪和青蛙成纤维细胞衍生的细胞系XTC-2中，T3上调Bteb 1 mRNA的动力学比Tr β A更快，Bteb 1 mRNA与BTEB 1蛋白表达增加相关。BTEB 1在体外与Tr β A启动子近端富含GC的序列结合。通过使用染色质免疫沉淀分析，我们表明，BTEB 1协会与Tr β A启动子在体内T3和发育阶段依赖性的方式。BTEB 1在XTC-2细胞中的诱导表达引起Tr β A基因的加速和增强的自身诱导。这种增强在BTEB 1的N-末端截短突变体中丢失。然而，破坏DNA结合的BTEB 1锌指的点突变并没有改变蛋白质对Tr β A自身诱导的活性，这表明BTEB 1可以通过蛋白质-蛋白质相互作用在这方面发挥作用。我们的研究结果支持这一假设，即BTEB 1协会与Tr β A启动子在体内，并增强自诱导，但这种行动并不依赖于它的DNA结合活性。立即早期基因的蛋白质产物之间的合作可能是驱动发育信号通路的共同机制。
Thyroid hormone (T-3) induces gene regulation programs necessary for tadpole metamorphosis. Among the earliest responses to T3 are the up-regulation of T3 receptor beta (TR beta; autoinduction) and BTEB1 (basic transcription element-binding protein 1). BTEB1 is a member of the Kruppel family of transcription factors that bind to GC-rich regions in gene promoters. The proximal promoter of the Xenopus laevis Tr beta A gene has seven GC-rich sequences, which led us to hypothesize that BTEB1 binds to and regulates Tr beta A. In tadpoles and the frog fibroblast-derived cell line XTC-2, T3 up-regulated Bteb1 mRNA with faster kinetics than Tr beta A, and Bteb1 mRNA correlated with increased BTEB1 protein expression. BTEB1 bound to GC-rich sequences in the proximal Tr beta A promoter in vitro. By using chromatin immunoprecipitation assay, we show that BTEB1 associates with the Tr beta A promoter in vivo in a T3 and developmental stage-dependent manner. Induced expression of BTEB1 in XTC-2 cells caused accelerated and enhanced autoinduction of the Tr beta A gene. This enhancement was lost in N-terminal truncated mutants of BTEB1. However, point mutations in the zinc fingers of BTEB1 that destroyed DNA binding did not alter the activity of the protein on Tr beta A autoinduction, suggesting that BTEB1 can function in this regard through protein-protein interactions. Our findings support the hypothesis that BTEB1 associates with the Tr beta A promoter in vivo and enhances autoinduction, but this action does not depend on its DNA binding activity. Cooperation among the protein products of immediate early genes may be a common mechanism for driving developmental signaling pathways.