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.
Chen
Xi
X
Gene Regulation Laboratory, Genome Institute of Singapore, Singapore 138672.
Xu
Han
H
Yuan
Ping
P
Fang
Fang
F
Huss
Mikael
M
Vega
Vinsensius B
VB
Wong
Eleanor
E
Orlov
Yuriy L
YL
Zhang
Weiwei
W
Jiang
Jianming
J
Loh
Yuin-Han
YH
Yeo
Hock Chuan
HC
Yeo
Zhen Xuan
ZX
Narang
Vipin
V
Govindarajan
Kunde Ramamoorthy
KR
Leong
Bernard
B
Shahab
Atif
A
Ruan
Yijun
Y
Bourque
Guillaume
G
Sung
Wing-Kin
WK
Clarke
Neil D
ND
Wei
Chia-Lin
CL
Ng
Huck-Hui
HH
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