An extended transcriptional network for pluripotency of embryonic stem cells
An extended transcriptional network for pluripotency of embryonic stem cells
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DOI：
10.1016/j.cell.2008.02.039
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发表时间：
2008-03-21
期刊：
影响因子：
64.5
通讯作者：
Orkin, Stuart H.
中科院分区：
文献类型：
--
作者：
Kim, Jonghwan;Chu, Jianlin;Orkin, Stuart H.
非常关注的集中在一系列的转录因子上，这些转录因子将人类或小鼠胚胎（ES）细胞保持在多能状态。为了对维持该状态的监管网络有更全面的了解，我们确定了九个转录因子的目标启动子，包括体细胞重编程因子（OCT4，SOX2，KLF4和C-MYC）等（Nanog，Dax1，rex1，Rex1，rex1，rex1，rex1，rex1，klf4和c-Myc） ZPF281和NAC1），在小鼠ES细胞中的全球尺度上。我们发现，靶基因分为两个类别：受限制因素限制的启动子往往是不活跃或抑制的，而受四个以上因素限制的启动子在多能状态下在很大程度上活跃，并在分化后被压抑。此外，我们提出了一个转录层次结构，用于重编程因素，并广泛区分C-MYC的靶标与其他因素。我们的数据为探索复杂网络维持多能性提供了资源。
Much attention has focused on a small set of transcription factors that maintain human or mouse embryonic stem (ES) cells in a pluripotent state. To gain a more complete understanding of the regulatory network that maintains this state, we identified target promoters of nine transcription factors, including somatic cell reprogramming factors (Oct4, Sox2, Klf4, and c-Myc) and others (Nanog, Dax1, Rex1, Zpf281, and Nac1), on a global scale in mouse ES cells. We found that target genes fall into two classes: promoters bound by few factors tend to be inactive or repressed, whereas promoters bound by more than four factors are largely active in the pluripotent state and become repressed upon differentiation. Furthermore, we propose a transcriptional hierarchy for reprogramming factors and broadly distinguish targets of c-Myc versus other factors. Our data provide a resource for exploration of the complex network maintaining pluripotency.