The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells.
Oct4 and Nanog are transcription factors required to maintain the pluripotency and self-renewal of embryonic stem (ES) cells. Using the chromatin immunoprecipitation paired-end ditags method, we mapped the binding sites of these factors in the mouse ES cell genome. We identified 1,083 and 3,006 high-confidence binding sites for Oct4 and Nanog, respectively. Comparative location analyses indicated that Oct4 and Nanog overlap substantially in their targets, and they are bound to genes in different configurations. Using de novo motif discovery algorithms, we defined the cis-acting elements mediating their respective binding to genomic sites. By integrating RNA interference-mediated depletion of Oct4 and Nanog with microarray expression profiling, we demonstrated that these factors can activate or suppress transcription. We further showed that common core downstream targets are important to keep ES cells from differentiating. The emerging picture is one in which Oct4 and Nanog control a cascade of pathways that are intricately connected to govern pluripotency, self-renewal, genome surveillance and cell fate determination.
Loh
Yuin-Han
YH
Gene Regulation Laboratory, Genome Institute of Singapore, Singapore 138672.
Wu
Qiang
Q
Chew
Joon-Lin
JL
Vega
Vinsensius B
VB
Zhang
Weiwei
W
Chen
Xi
X
Bourque
Guillaume
G
George
Joshy
J
Leong
Bernard
B
Liu
Jun
J
Wong
Kee-Yew
KY
Sung
Ken W
KW
Lee
Charlie W H
CW
Zhao
Xiao-Dong
XD
Chiu
Kuo-Ping
KP
Lipovich
Leonard
L
Kuznetsov
Vladimir A
VA
Robson
Paul
P
Stanton
Lawrence W
LW
Wei
Chia-Lin
CL
Ruan
Yijun
Y
Lim
Bing
B
Ng
Huck-Hui
HH
D000818:Animals; D004268:DNA-Binding Proteins / Q000502:physiology*; D004622:Embryo, Mammalian / Q000166:cytology* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D018398:Homeodomain Proteins / Q000502:physiology*; D006801:Humans; D051379:Mice; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3 / Q000502:physiology*; D034622:RNA Interference; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology*
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse