TY - JOUR
T1 - Uncovering Early Response of Gene Regulatory Networks in ESCs by Systematic Induction of Transcription Factors
AU - Nishiyama, Akira
AU - Xin, Li
AU - Sharov, Alexei A.
AU - Thomas, Marshall
AU - Mowrer, Gregory
AU - Meyers, Emily
AU - Piao, Yulan
AU - Mehta, Samir
AU - Yee, Sarah
AU - Nakatake, Yuhki
AU - Stagg, Carole
AU - Sharova, Lioudmila
AU - Correa-Cerro, Lina S.
AU - Bassey, Uwem
AU - Hoang, Hien
AU - Kim, Eugene
AU - Tapnio, Richard
AU - Qian, Yong
AU - Dudekula, Dawood
AU - Zalzman, Michal
AU - Li, Manxiang
AU - Falco, Geppino
AU - Yang, Hsih Te
AU - Lee, Sung Lim
AU - Monti, Manuela
AU - Stanghellini, Ilaria
AU - Islam, Md Nurul
AU - Nagaraja, Ramaiah
AU - Goldberg, Ilya
AU - Wang, Weidong
AU - Longo, Dan L.
AU - Schlessinger, David
AU - Ko, Minoru S.H.
N1 - Funding Information:
We thank Dr. Hitoshi Niwa for providing the Tet-inducible vector system and some cDNA clones and for discussion. This research was supported entirely by the Intramural Research Program of the NIH, National Institute on Aging.
PY - 2009/10/2
Y1 - 2009/10/2
N2 - 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.
AB - 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.
KW - STEMCELL
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U2 - 10.1016/j.stem.2009.07.012
DO - 10.1016/j.stem.2009.07.012
M3 - Article
C2 - 19796622
AN - SCOPUS:70349325798
SN - 1934-5909
VL - 5
SP - 420
EP - 433
JO - Cell stem cell
JF - Cell stem cell
IS - 4
ER -