Uncovering early response of gene regulatory networks in ESCs by systematic induction of transcription factors.
Uncovering early response of gene regulatory networks in ESCs by systematic induction of transcription factors.
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通过系统诱导转录因子，揭示了ESC中基因调节网络的早期反应。
DOI：
10.1016/j.stem.2009.07.012
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发表时间：
2009-10-02
期刊：
影响因子：
23.9
通讯作者：
Ko MS
中科院分区：
文献类型：
--
作者：
Nishiyama A;Xin L;Sharov AA;Thomas M;Mowrer G;Meyers E;Piao Y;Mehta S;Yee S;Nakatake Y;Stagg C;Sharova L;Correa-Cerro LS;Bassey U;Hoang H;Kim E;Tapnio R;Qian Y;Dudekula D;Zalzman M;Li M;Falco G;Yang HT;Lee SL;Monti M;Stanghellini I;Islam MN;Nagaraja R;Goldberg I;Wang W;Longo DL;Schlessinger D;Ko MS
为了检测转录因子（TF）网络，我们创建了小鼠ES细胞系，在每个细胞系中，50个标记有FLAG片段的TF中的一个被插入到一个普遍可控的四环素抑制位点。在50个tf中，Cdx2在ES细胞中引起最广泛的转录组扰动，其次是Esx1、Sox9、Tcf3、Klf4和Gata3。ChIP-Seq显示CDX2与上调靶基因的启动子结合。相比之下，CDX2下调的基因不显示CDX2结合，但富含POU5F1、SOX2和NANOG的结合位点。这些核心tf结合位点的基因也通过诱导至少15个其他tf而下调，这表明干扰核心tf与其靶基因的结合介导了胚胎干细胞分化的共同初始步骤。这些胚胎干细胞系为研究胚胎干细胞和小鼠的生物网络提供了基础资源。
To examine transcription factor (TF) network(s), we created mouse ES cell lines, in each of which one of 50 TFs tagged with a FLAG moiety is inserted into a ubiquitously controllable tetracycline-repressible locus. Of the 50 TFs, Cdx2 provoked the most extensive transcriptome perturbation in ES cells, followed by Esx1, Sox9, Tcf3, Klf4, and Gata3. ChIP-Seq revealed that CDX2 binds to promoters of up-regulated target genes. By contrast, genes down-regulated by CDX2 did not show CDX2 binding, but were enriched with binding sites for POU5F1, SOX2, and NANOG. Genes with binding sites for these core TFs were also down-regulated by the induction of at least 15 other TFs, suggesting a common initial step for ES cell differentiation mediated by interference with the binding of core TFs to their target genes. These ES cell lines provide a fundamental resource to study biological networks in ES cells and mice.
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