An expanded Oct4 interaction network: implications for stem cell biology, development, and disease.

An expanded Oct4 interaction network: implications for stem cell biology, development, and disease.
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DOI:
10.1016/j.stem.2010.03.004
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发表时间:
2010-04-02
期刊:
影响因子:
23.9
通讯作者:
Choudhary J
Choudhary J
中科院分区:
医学1区
文献类型:
--
作者:
Pardo M;Lang B;Yu L;Prosser H;Bradley A;Babu MM;Choudhary J

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转录因子Oct4在胚胎干细胞特性及重编程中起关键作用。对其相关因子的了解应能阐明多能性状态是如何建立和调控的。在此,我们在小鼠胚胎干细胞中鉴定出一组数量大幅增加的Oct4结合蛋白。我们发现Oct4与多种蛋白质相关联,包括基因表达的调节因子和Oct4功能的调节因子。其半数相关因子受Oct4自身或其他干细胞转录因子的转录调控,而三分之一在细胞分化时表达发生显著变化。迄今为止研究的大多数与Oct4相关的蛋白质在发生突变时都表现出早期致死表型。一部分人类同源基因与遗传性发育障碍有关或可导致癌症。Oct4相互作用组为剖析Oct4功能机制、阐明多能性和发育的基础以及确定潜在的其他重编程因子提供了资源。 ►Oct4与大量多种蛋白质相关联 ►Oct4的半数相关因子受关键干细胞转录因子调控 ►大多数Oct4结合蛋白是小鼠早期发育所必需的 ►一些Oct4相关因子与人类发育障碍或癌症有关
The transcription factor Oct4 is key in embryonic stem cell identity and reprogramming. Insight into its partners should illuminate how the pluripotent state is established and regulated. Here, we identify a considerably expanded set of Oct4-binding proteins in mouse embryonic stem cells. We find that Oct4 associates with a varied set of proteins including regulators of gene expression and modulators of Oct4 function. Half of its partners are transcriptionally regulated by Oct4 itself or other stem cell transcription factors, whereas one-third display a significant change in expression upon cell differentiation. The majority of Oct4-associated proteins studied to date show an early lethal phenotype when mutated. A fraction of the human orthologs is associated with inherited developmental disorders or causative of cancer. The Oct4 interactome provides a resource for dissecting mechanisms of Oct4 function, enlightening the basis of pluripotency and development, and identifying potential additional reprogramming factors. ► Oct4 associates with a large varied set of proteins ► Half of Oct4's partners are regulated by key stem cell transcription factors ► Most Oct4 binding proteins are required for early development in mouse ► Some Oct4 partners are associated with human developmental disorders or cancer
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发表时间: 2009-01
影响因子: 14.9
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发表时间: 2003-06-24
影响因子: 11.1
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发表时间: 1997-11-01
影响因子: 2.7
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