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首页> 外文期刊>Molecular and Cellular Biology >Repression of Nanog Gene Transcription by Tcf3 Limits Embryonic Stem Cell Self-Renewal
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Repression of Nanog Gene Transcription by Tcf3 Limits Embryonic Stem Cell Self-Renewal

机译：Tcf3抑制Nanog基因转录限制了胚胎干细胞的自我更新。

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The dual function of stem cells requires them not only to form new stem cells through self-renewal but also to form lineage-committed cells through differentiation. Embryonic stem cells (ESC), which are derived from the blastocyst inner cell mass, retain properties of self-renewal and the potential for lineage commitment. To balance self-renewal and differentiation, ESC must carefully control the levels of several transcription factors, including Nanog, Sox2, and Oct4. While molecular mechanisms promoting transcription of these genes have been described, mechanisms preventing excessive levels in self-renewing ESC remain unknown. By examining the function of the TCF family of transcription factors in ESC, we have found that Tcf3 is necessary to limit the steady-state levels of Nanog mRNA, protein, and promoter activity in self-renewing ESC. Chromatin immunoprecipitation and promoter reporter assays showed that Tcf3 bound to a promoter regulatory region of the Nanog gene and repressed its transcriptional activity in ESC through a Groucho interaction domain-dependent process. The absence of Tcf3 caused delayed differentiation of ESC in vitro as elevated Nanog levels persisted through 5 days of embryoid body formation. These new data support a model wherein Tcf3-mediated control of Nanog levels allows stem cells to balance the creation of lineage-committed and undifferentiated cells.
机译：干细胞的双重功能不仅要求它们通过自我更新形成新的干细胞，而且还需要通过分化形成谱系定型的细胞。胚胎干细胞（ESC）源自胚泡内部细胞团，保留了自我更新的特性和沿袭承诺的潜力。为了平衡自我更新和分化，ESC必须仔细控制几种转录因子的水平，包括Nanog，Sox2和Oct4。虽然已经描述了促进这些基因转录的分子机制，但是防止自我更新ESC中过量水平的机制仍然未知。通过检查TCF家族的转录因子在ESC中的功能，我们发现Tcf3对于限制自我更新ESC中Nanog mRNA，蛋白质和启动子活性的稳态水平是必需的。染色质免疫沉淀和启动子报告基因检测表明，Tcf3与Nanog基因的启动子调节区结合，并通过Groucho相互作用域依赖性过程抑制了其在ESC中的转录活性。 Tcf3的缺乏导致体外ESC的分化延迟，因为Nanog水平升高持续到拟胚体形成5天。这些新数据支持了一个模型，其中Tcf3介导的Nanog水平控制使干细胞能够平衡谱系承诺和未分化细胞的产生。

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