A Myc network accounts for similarities between embryonic stem and cancer cell transcription programs.

A Myc network accounts for similarities between embryonic stem and cancer cell transcription programs.
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DOI:
10.1016/j.cell.2010.09.010
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发表时间:
2010-10-15
期刊:
影响因子:
64.5
通讯作者:
Orkin SH
Orkin SH
中科院分区:
生物学1区
文献类型:
--
作者:
Kim J;Woo AJ;Chu J;Snow JW;Fujiwara Y;Kim CG;Cantor AB;Orkin SH

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c-Myc(Myc)是胚胎干(ES)细胞、体细胞重编程和癌症中重要的转录调节因子。在这里,我们通过结合蛋白质-蛋白质和蛋白质-DNA相互作用的研究,确定了在ES细胞中以Myc为中心的调控网络,并表明Myc与NuA 4复合物相互作用,NuA 4复合物是ES细胞身份的调节剂。结合调控网络信息,我们定义了三个ES细胞模块(核心,Polycomb和Myc),并表明这些模块在功能上是可分离的,说明整个ES细胞转录程序由不同的单元组成。以这些模块为分析工具,我们重新评估了ES细胞特征与癌症或癌症干细胞之间的联系。我们发现,Myc模块,独立于核心模块,在各种癌症中是活跃的,并预测癌症的结果。癌症和ES细胞特征的明显相似性在很大程度上反映了Myc调控网络的普遍性质。
c-Myc (Myc) is an important transcriptional regulator in embryonic stem (ES) cells, somatic cell reprogramming, and cancer. Here, we identify a Myc-centered regulatory network in ES cells by combining protein-protein and protein-DNA interaction studies, and show that Myc interacts with the NuA4 complex, a regulator of ES cell identity. In combination with regulatory network information, we define three ES cell modules (Core, Polycomb, and Myc), and show that the modules are functionally separable, illustrating that the overall ES cell transcription program is comprised of distinct units. With these modules as an analytical tool, we have reassessed the hypothesis linking an ES cell signature with cancer or cancer stem cells. We find that the Myc module, independent of the Core module, is active in various cancers and predicts cancer outcome. The apparent similarity of cancer and ES cell signatures reflects in large part the pervasive nature of Myc regulatory network.
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