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首页> 外文期刊>Cell Research >Xom interacts with and stimulates transcriptional activity of LEF1/TCFs: implications for ventral cell fate determination during vertebrate embryogenesis
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Xom interacts with and stimulates transcriptional activity of LEF1/TCFs: implications for ventral cell fate determination during vertebrate embryogenesis

机译：Xom与LEF1 / TCF相互作用并刺激其转录活性：在脊椎动物胚胎发生过程中对腹侧细胞命运决定的意义

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摘要

LEF1/TCFs are high mobility group box-containing transcriptional factors mediating canonical Wnt/β-catenin signaling during early embryogenesis and tumorigenesis. β-Catenin forms a complex with LEF1/TCFs and transactivates LEF1/TCF-mediated transcriptions during dorsalization. Although LEF-mediated transcription is also implicated in ventralization, the underlying molecular mechanism is not well understood. Using the vertebrate Xenopus laevis model system, we found that Xom, which is a ventralizing homeobox protein with dual roles of transcriptional activation and repression, forms a complex with LEF1/TCF through its homeodomain and transactivates LEF1/TCF-mediated transcription through its N-terminal transactivation domain (TAD). Our data show that Xom lacking the N-terminal TAD fails to transactivate ventral genes, such as BMP4 and Xom itself, but retains the ability to suppress transcriptional activation of dorsal gene promoters, such as the Goosecoid promoter, indicating that transactivation and repression are separable functions of Xom. It has been postulated that Xom forms a positive re-enforcement loop with BMP4 to promote ventralization and to suppress dorsal gene expression. Consistent with an essential role of Xom transactivation of LEF1/TCFs during early embryogenesis, we found that expression of the dominant-negative Xom mutant that lacks the TAD fails to re-enforce the ventral signaling of BMP4 and causes a catastrophic effect during gastrulation. Our data suggest that the functional interaction of Xom and LEF1/TCF-factors is essential for ventral cell fate determination and that LEF1/TCF factors may function as a point of convergence to mediate the combined signaling of Wnt/β-catenin and BMP4/Xom pathways during early embryogenesis.
机译：LEF1 / TCFs是包含高迁移率基团框的转录因子，可在早期胚胎发生和肿瘤发生过程中介导经典的Wnt /β-catenin信号传导。 β-连环蛋白与LEF1 / TCF形成复合物，并在背侧化过程中激活LEF1 / TCF介导的转录。尽管LEF介导的转录也与腹侧化有关，但潜在的分子机制尚不清楚。使用脊椎动物非洲爪蟾（Xenopus laevis）模型系统，我们发现Xom是一种腹侧同源盒蛋白，具有转录激活和抑制的双重作用，通过其同源域与LEF1 / TCF形成复合体，并通过其N-激活LEF1 / TCF介导的转录。末端反式激活域（TAD）。我们的数据显示，缺少N末端TAD的Xom未能使腹侧基因（如BMP4和Xom本身）反式激活，但保留了抑制背侧基因启动子（如鹅肝启动子）的转录激活的能力，表明反式激活和抑制是可分离的Xom的功能。据推测，Xom与BMP4形成一个正的增强环，以促进腹侧化并抑制背侧基因表达。与早期胚胎发生过程中LEF1 / TCF的Xom反式激活的重要作用相一致，我们发现缺乏TAD的显性负Xom突变体的表达不能增强BMP4的腹侧信号传导，并在胃肠形成过程中造成灾难性影响。我们的数据表明，Xom和LEF1 / TCF因子的功能相互作用对于确定腹侧细胞的命运至关重要，并且LEF1 / TCF因子可能作为汇聚点来介导Wnt /β-catenin和BMP4 / Xom的联合信号传导。早期胚胎发生的途径。

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