Integration of external signaling pathways with the core transcriptional network in embryonic stem cells.
Transcription factors (TFs) and their specific interactions with targets are crucial for specifying gene-expression programs. To gain insights into the transcriptional regulatory networks in embryonic stem (ES) cells, we use chromatin immunoprecipitation coupled with ultra-high-throughput DNA sequencing (ChIP-seq) to map the locations of 13 sequence-specific TFs (Nanog, Oct4, STAT3, Smad1, Sox2, Zfx, c-Myc, n-Myc, Klf4, Esrrb, Tcfcp2l1, E2f1, and CTCF) and 2 transcription regulators (p300 and Suz12). These factors are known to play different roles in ES-cell biology as components of the LIF and BMP signaling pathways, self-renewal regulators, and key reprogramming factors. Our study provides insights into the integration of the signaling pathways into the ES-cell-specific transcription circuitries. Intriguingly, we find specific genomic regions extensively targeted by different TFs. Collectively, the comprehensive mapping of TF-binding sites identifies important features of the transcriptional regulatory networks that define ES-cell identity.
Gene Regulation Laboratory, Genome Institute of Singapore, Singapore 138672.
Xi
X
Chen
Han
H
Xu
Ping
P
Yuan
Fang
F
Fang
Mikael
M
Huss
Vinsensius B
VB
Vega
Eleanor
E
Wong
Yuriy L
YL
Orlov
Weiwei
W
Zhang
Jianming
J
Jiang
Yuin-Han
YH
Loh
Hock Chuan
HC
Yeo
Zhen Xuan
ZX
Yeo
Vipin
V
Narang
Kunde Ramamoorthy
KR
Govindarajan
Bernard
B
Leong
Atif
A
Shahab
Yijun
Y
Ruan
Guillaume
G
Bourque
Wing-Kin
WK
Sung
Neil D
ND
Clarke
Chia-Lin
CL
Wei
Huck-Hui
HH
Ng
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D047369:Chromatin Immunoprecipitation; D053595:Embryonic Stem Cells / Q000378:metabolism*; D053263:Gene Regulatory Networks; D016678:Genome; D000090062:Kruppel-Like Factor 4; D051379:Mice; D046912:Multiprotein Complexes; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism
C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D046912:Multiprotein Complexes; D014157:Transcription Factors