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

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, followe...

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Published in:	Cell stem cell Vol. 5; no. 4; p. 420
Main Authors:	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
Format:	Journal Article
Language:	English
Published:	United States 02.10.2009
Subjects:	Animals Basic Helix-Loop-Helix Transcription Factors - genetics Basic Helix-Loop-Helix Transcription Factors - metabolism Basic Helix-Loop-Helix Transcription Factors - physiology CDX2 Transcription Factor Cell Differentiation - genetics Cell Differentiation - physiology Cell Line Chromatin Immunoprecipitation Embryonic Stem Cells - cytology Embryonic Stem Cells - metabolism GATA3 Transcription Factor - genetics GATA3 Transcription Factor - metabolism GATA3 Transcription Factor - physiology Gene Regulatory Networks - genetics Gene Regulatory Networks - physiology Homeodomain Proteins - genetics Homeodomain Proteins - metabolism Homeodomain Proteins - physiology Immunoprecipitation Kruppel-Like Factor 4 Kruppel-Like Transcription Factors - genetics Kruppel-Like Transcription Factors - metabolism Kruppel-Like Transcription Factors - physiology Mice Oligonucleotide Array Sequence Analysis Proto-Oncogene Proteins - genetics Proto-Oncogene Proteins - metabolism Proto-Oncogene Proteins - physiology SOX9 Transcription Factor - genetics SOX9 Transcription Factor - metabolism SOX9 Transcription Factor - physiology Transcription Factors - genetics Transcription Factors - metabolism Transcription Factors - physiology
ISSN:	1875-9777, 1875-9777
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1875-9777 1875-9777
DOI:	10.1016/j.stem.2009.07.012