Cross-regulation of the Nanog and Cdx2 promoters
Cross-regulation of the Nanog and Cdx2 promoters
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DOI：
10.1038/cr.2009.79
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发表时间：
2009-09-01
期刊：
影响因子：
44.1
通讯作者：
Daley, George Q.
中科院分区：
文献类型：
--
作者：
Chen, Lingyi;Yabuuchi, Akiko;Daley, George Q.
哺乳动物胚胎中的第一个细胞命运选择，即内细胞团(ICM)和滋养外胚层(TE)的分离，受转录因子Oct4和CDx2相互拮抗的影响，而多能因子Nanog则是决定上胚层的关键。我们分析了Nanog和CDX2的启动子，发现这两个转录因子同样是相互调控的。利用具有条件TE分化的胚胎干细胞系，我们发现Nanog过表达抑制TE标记的上调，而Nanog基因敲除则上调TE标记的表达。我们进一步证明了Nanog和Cdx2相互结合并抑制了彼此的启动子。然而，虽然Nanog基因敲除导致ICM中可检测到CDX2的表达，但我们没有观察到明显的囊胚发育中断，这表明Nanog在ICM和TE的分离中起着从属于Oct4的作用。
The first cell fate choice in the mammalian embryo, the segregation of the inner cell mass (ICM) and trophectoderm (TE), is regulated by the mutually antagonistic effects of the transcription factors, Oct4 and Cdx2, while the pluripotency factor, Nanog, is essential to specify the epiblast. We have analyzed the promoters of Nanog and Cdx2, and have found that these two transcription factors are likewise regulated reciprocally. Using an embryonic stem cell line with conditional TE differentiation, we show that Nanog overexpression suppresses the upregulation of TE markers, while Nanog knockdown upregulates the expression of TE markers. We further show that Nanog and Cdx2 bind to and repress each other's promoters. However, whereas Nanog knockout results in detectable Cdx2 expression in the ICM, we observe no overt disruption of blastocyst development, indicating that Nanog plays a subservient role to Oct4 in segregation of the ICM and TE.