Uncovering Early Response of Gene Regulatory Networks in ESCs by Systematic Induction of Transcription Factors

Akira Nishiyama, Li Xin, Alexei A. Sharov, Marshall Thomas, Gregory Mowrer, Emily Meyers, Yulan Piao, Samir Mehta, Sarah Yee, Yuhki Nakatake, Carole Stagg, Lioudmila Sharova, Lina S. Correa-Cerro, Uwem Bassey, Hien Hoang, Eugene Kim, Richard Tapnio, Yong Qian, Dawood Dudekula, Michal ZalzmanManxiang Li, Geppino Falco, Hsih Te Yang, Sung Lim Lee, Manuela Monti, Ilaria Stanghellini, Md Nurul Islam, Ramaiah Nagaraja, Ilya Goldberg, Weidong Wang, Dan L. Longo, David Schlessinger, Minoru S.H. Ko

Research output: Contribution to journalArticle

141 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)420-433
Number of pages14
JournalCell stem cell
Volume5
Issue number4
DOIs
Publication statusPublished - 2009 Oct 2

Keywords

  • STEMCELL

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology

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    Nishiyama, A., Xin, L., Sharov, A. A., Thomas, M., Mowrer, G., Meyers, E., Piao, Y., Mehta, S., Yee, S., Nakatake, Y., Stagg, C., Sharova, L., Correa-Cerro, L. S., Bassey, U., Hoang, H., Kim, E., Tapnio, R., Qian, Y., Dudekula, D., ... Ko, M. S. H. (2009). Uncovering Early Response of Gene Regulatory Networks in ESCs by Systematic Induction of Transcription Factors. Cell stem cell, 5(4), 420-433. https://doi.org/10.1016/j.stem.2009.07.012