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Publication : Uncovering early response of gene regulatory networks in ESCs by systematic induction of transcription factors.

First Author  Nishiyama A Year  2009
Journal  Cell Stem Cell Volume  5
Issue  4 Pages  420-33
PubMed ID  19796622 Mgi Jnum  J:154112
Mgi Id  MGI:4367296 Doi  10.1016/j.stem.2009.07.012
Citation  Nishiyama A, et al. (2009) Uncovering early response of gene regulatory networks in ESCs by systematic induction of transcription factors. Cell Stem Cell 5(4):420-33
abstractText  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.
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