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首页> 外文期刊>Nature >Eya protein phosphatase activity regulates Six1-Dach-Eya transcriptional effects in mammalian organogenesis
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Eya protein phosphatase activity regulates Six1-Dach-Eya transcriptional effects in mammalian organogenesis

机译：Eya蛋白磷酸酶活性调节哺乳动物器官发生中的Six1-Dach-Eya转录作用。

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摘要

The precise mechanistic relationship between gene activation and repression events is a central question in mammalian qrganogenesis, as exemplified by the evolutionarily conserved sine oculis (Six), eyes absent (Eya) and dachshund (Dach) network of genetically interacting proteins. Here, we report that Six1 is required for the development of murine kidney, muscle and inner ear, and that it exhibits synergistic genetic interactions with Eya factors. We demonstrate that the Eya family has a protein phosphatase function, and that its enzymatic activity is required for regulating genes encoding growth control and signalling molecules, modulating precursor cell proliferation. The phosphatase function of Eya switches the function of Six1-Dach from repression to activation, causing transcriptional activation through recruitment of co-activators. The gene-specific recruitment of a co-activator with intrinsic phosphatase activity provides a molecular mechanism for activation of specific gene targets, including those regulating precursor cell proliferation and survival in mammalian organogenesis.
机译：基因激活与抑制事件之间精确的机制关系是哺乳动物qrganogenesis中的一个中心问题，例如遗传上互作蛋白质的进化保守正弦球（Six），无眼（Eya）和腊肠（Dachshund）网络就是例证。在这里，我们报告Six1是小鼠肾脏，肌肉和内耳的发展所必需的，并且它表现出与Eya因子的协同遗传相互作用。我们证明Eya家族具有蛋白质磷酸酶功能，并且其酶促活性是调节编码生长控制和信号分子，调节前体细胞增殖的基因所必需的。 Eya的磷酸酶功能将Six1-Dach的功能从抑制状态转变为激活状态，从而通过募集共激活剂而引起转录激活。具有固有磷酸酶活性的共激活因子的基因特异性募集提供了激活特定基因靶标的分子机制，包括调节哺乳动物器官发生中前体细胞增殖和存活的那些靶标。

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