Nishiyama Akira, Xin Li, Sharov Alexei A, Thomas Marshall, Mowrer Gregory, Meyers Emily, Piao Yulan, Mehta Samir, Yee Sarah, Nakatake Yuhki, Stagg Carole, Sharova Lioudmila, Correa-Cerro Lina S, Bassey Uwem, Hoang Hien, Kim Eugene, Tapnio Richard, Qian Yong, Dudekula Dawood, Zalzman Michal, Li Manxiang, Falco Geppino, Yang Hsih-Te, Lee Sung-Lim, Monti Manuela, Stanghellini Ilaria, Islam Md Nurul, Nagaraja Ramaiah, Goldberg Ilya, Wang Weidong, Longo Dan L, Schlessinger David, Ko Minoru S H
National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
Cell Stem Cell. 2009 Oct 2;5(4):420-33. doi: 10.1016/j.stem.2009.07.012.
To examine transcription factor (TF) network(s), we created mouse ESC lines, in each of which 1 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 ESCs, followed by Esx1, Sox9, Tcf3, Klf4, and Gata3. ChIP-Seq revealed that CDX2 binds to promoters of upregulated target genes. By contrast, genes downregulated 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 downregulated by the induction of at least 15 other TFs, suggesting a common initial step for ESC differentiation mediated by interference with the binding of core TFs to their target genes. These ESC lines provide a fundamental resource to study biological networks in ESCs and mice.
为了研究转录因子（TF）网络，我们构建了小鼠胚胎干细胞（ESC）系，其中50个带有FLAG标签的TF中的每一个都被插入到一个普遍可控的四环素抑制位点。在这50个TF中，Cdx2在ESC中引发了最广泛的转录组扰动，其次是Esx1、Sox9、Tcf3、Klf4和Gata3。染色质免疫沉淀测序（ChIP-Seq）显示CDX2与上调的靶基因启动子结合。相比之下，被CDX2下调的基因未显示CDX2结合，但富含POU5F1、SOX2和NANOG的结合位点。具有这些核心TF结合位点的基因也被至少15种其他TF的诱导下调，这表明ESC分化的一个共同初始步骤是通过干扰核心TF与其靶基因的结合来介导的。这些ESC系为研究ESC和小鼠中的生物网络提供了一个基础资源。
