The Role of Homeobox Protein Distal-Less 3 and Its Interaction with ETS2 in Regulating Bovine Interferon-Tau Gene Expression-Synergistic Transcriptional Activation with ETS21
The Role of Homeobox Protein Distal-Less 3 and Its Interaction with ETS2 in Regulating Bovine Interferon-Tau Gene Expression-Synergistic Transcriptional Activation with ETS21
复制标题
同源盒蛋白Distal-Less 3及其与ETS2的相互作用在调节牛干扰素-Tau基因表达中的作用-与ETS21的协同转录激活
作者：
T. Ezashi;P. Das;Rangan Gupta;Angela M. Walker;R. Roberts
摘要 Distal-less 3 (DLX3) 是小鼠胎盘发育所需的同源域转录因子，可适度反式激活人绒毛膜癌细胞中的 hCG-α 亚基基因 (hCGA) 表达。由于 hCG 和干扰素 tau (IFNT) 分别在灵长类动物和反刍动物的滋养外胚层中表达，因此我们检验了 DLX3 调节 IFNT (IFNT) 基因的假设。与荧光素酶 (luc) 报告基因连接的牛 IFNT1 启动子（-457 至 +66）通过在人 JAr 细胞中过表达 DLX3 被反式激活约 20 倍。通过截短或诱变消除潜在的DLX3结合位点（-54 GATAATGAG -46）消除了这种效应。包含该位点的序列（-59至-44）特异性结合DLX3。 DLX3 和 ETS2（已知是 IFNT 表达的关键调节因子）的共表达使报告基因活性增加了 250 倍以上，而删除已建立的 ETS2 位点（-79 至 -70）则消除了 DLX3 反式激活该基因的能力。相反，DLX3位点的突变显着降低了ETS2的反式激活作用。 DLX3 和 ETS2 在 JAr 细胞和产生 IFNT 的牛滋养层细胞系 CT-1 中共表达。两者可以作为来自 CT-1 细胞的复合物一起免疫沉淀，并且 RNAi 介导的 DLX3 表达的部分敲低使 IFNT 的产生减少了约 50+。总之，这些结果表明DLX3通过与IFNT启动子上的ETS2结合在控制IFNT基因表达中发挥核心作用。
Abstract Distal-less 3 (DLX3), a homeodomain transcription factor required for placental development in the mouse, modestly transactivates hCG-alpha subunit gene (hCGA) expression in human choriocarcinoma cells. Because hCG and interferon-tau (IFNT) are expressed in trophectoderm of primates and ruminants, respectively, we have tested the hypothesis that DLX3 regulates the genes for IFNT (IFNT). A bovine IFNT1 promoter (−457 to +66), linked to a luciferase (luc) reporter, was transactivated approximately 20-fold by overexpressing DLX3 in human JAr cells. Elimination of a potential DLX3-binding site (−54 GATAATGAG −46) by either truncation or mutagenesis abolished this effect. A sequence (−59 to −44) encompassing this site bound DLX3 specifically. Coexpression of DLX3 and ETS2, which is known to be a key regulator of IFNT expression, increased reporter activity by more than 250-fold, whereas deletion of the established ETS2 site (−79 to −70) eliminated the ability of DLX3 to transactivate the gene. Conversely, mutation of the DLX3 site significantly reduced the transactivational effects of ETS2. Both DLX3 and ETS2 are coexpressed in JAr cells and in an IFNT-producing, bovine trophoblast cell line, CT-1. The two can be immunoprecipitated together as a complex from CT-1 cells, and RNAi-mediated, partial knockdown of DLX3 expression reduced the production of IFNT by approximately 50+. Together, these results suggest that DLX3 has a central role in controlling IFNT gene expression by associating with ETS2 on the IFNT promoter.
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DOI：
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DOI：
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影响因子：
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