Ronin Is Essential for Embryogenesis and the Pluripotency of Mouse Embryonic Stem Cells
Ronin Is Essential for Embryogenesis and the Pluripotency of Mouse Embryonic Stem Cells
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DOI：
10.1016/j.cell.2008.08.002
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发表时间：
2008-08
期刊：
影响因子：
64.5
通讯作者：
M. Déjosez;J. Krumenacker;L. Zitur;M. Passeri;Li-Fang Chu;Songyang Zhou;J. Thomson;T. Zwaka
中科院分区：
文献类型：
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作者：
M. Déjosez;J. Krumenacker;L. Zitur;M. Passeri;Li-Fang Chu;Songyang Zhou;J. Thomson;T. Zwaka
多能性是一种独特的生物学状态，允许细胞分化成任何组织类型。在这里，我们描述了一个候选的多能性因子，Ronin，具有THAP结构域，这是与序列特异性DNA结合和基因表达的表观遗传沉默。Ronin主要在小鼠胚胎发育的最早阶段表达，其在小鼠中的缺陷产生围产期致死和内细胞团缺陷。Ronin的条件性敲除阻止ES细胞的生长，而Ronin的强制表达允许ES细胞在通常不促进自我更新的条件下增殖而不分化。异位表达也部分补偿了Oct 4敲低的影响。我们证明，Ronin直接结合到HCF-1，一个关键的转录调节因子。我们的研究结果确定Ronin作为胚胎发生和ES细胞多能性的基本因素。它与HCF-1的相关性提示了多能细胞中基因抑制的表观遗传机制。
Pluripotency is a unique biological state that allows cells to differentiate into any tissue type. Here we describe a candidate pluripotency factor, Ronin, that possesses a THAP domain, which is associated with sequence-specific DNA binding and epigenetic silencing of gene expression. Ronin is expressed primarily during the earliest stages of murine embryonic development, and its deficiency in mice produces periimplantational lethality and defects in the inner cell mass. Conditional knockout of Ronin prevents the growth of ES cells while forced expression of Ronin allows ES cells to proliferate without differentiation under conditions that normally do not promote self-renewal. Ectopic expression also partly compensates for the effects ofOct4knockdown. We demonstrate that Ronin binds directly to HCF-1, a key transcriptional regulator. Our findings identify Ronin as an essential factor underlying embryogenesis and ES cell pluripotency. Its association with HCF-1 suggests an epigenetic mechanism of gene repression in pluripotent cells.