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, 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.
Nishiyama
Akira
A
National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
Xin
Li
L
Sharov
Alexei A
AA
Thomas
Marshall
M
Mowrer
Gregory
G
Meyers
Emily
E
Piao
Yulan
Y
Mehta
Samir
S
Yee
Sarah
S
Nakatake
Yuhki
Y
Stagg
Carole
C
Sharova
Lioudmila
L
Correa-Cerro
Lina S
LS
Bassey
Uwem
U
Hoang
Hien
H
Kim
Eugene
E
Tapnio
Richard
R
Qian
Yong
Y
Dudekula
Dawood
D
Zalzman
Michal
M
Li
Manxiang
M
Falco
Geppino
G
Yang
Hsih-Te
HT
Lee
Sung-Lim
SL
Monti
Manuela
M
Stanghellini
Ilaria
I
Islam
Md Nurul
MN
Nagaraja
Ramaiah
R
Goldberg
Ilya
I
Wang
Weidong
W
Longo
Dan L
DL
Schlessinger
David
D
Ko
Minoru S H
MS
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D000071616:CDX2 Transcription Factor; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D053263:Gene Regulatory Networks / Q000235:genetics / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D047468:Immunoprecipitation; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D051792:Basic Helix-Loop-Helix Proteins; D000071616:CDX2 Transcription Factor; D050990:GATA3 Transcription Factor; D018398:Homeodomain Proteins; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D011518:Proto-Oncogene Proteins; D055758:SOX9 Transcription Factor; D014157:Transcription Factors; C487514:Cdx2 protein, mouse; C107475:Esx1 protein, mouse; C000715468:Klf4 protein, mouse; C527933:Sox9 protein, mouse; C075668:Tcf3 protein, mouse