title: The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells.
abstract: 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.
authors.affiliation: Gene Regulation Laboratory, Genome Institute of Singapore, Singapore 138672.
authors.forename: Yuin-Han
authors.initials: YH
authors.lastname: Loh
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wu
authors.forename: Joon-Lin
authors.initials: JL
authors.lastname: Chew
authors.forename: Vinsensius B
authors.initials: VB
authors.lastname: Vega
authors.forename: Weiwei
authors.initials: W
authors.lastname: Zhang
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.forename: Guillaume
authors.initials: G
authors.lastname: Bourque
authors.forename: Joshy
authors.initials: J
authors.lastname: George
authors.forename: Bernard
authors.initials: B
authors.lastname: Leong
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.forename: Kee-Yew
authors.initials: KY
authors.lastname: Wong
authors.forename: Ken W
authors.initials: KW
authors.lastname: Sung
authors.forename: Charlie W H
authors.initials: CW
authors.lastname: Lee
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Zhao
authors.forename: Kuo-Ping
authors.initials: KP
authors.lastname: Chiu
authors.forename: Leonard
authors.initials: L
authors.lastname: Lipovich
authors.forename: Vladimir A
authors.initials: VA
authors.lastname: Kuznetsov
authors.forename: Paul
authors.initials: P
authors.lastname: Robson
authors.forename: Lawrence W
authors.initials: LW
authors.lastname: Stanton
authors.forename: Chia-Lin
authors.initials: CL
authors.lastname: Wei
authors.forename: Yijun
authors.initials: Y
authors.lastname: Ruan
authors.forename: Bing
authors.initials: B
authors.lastname: Lim
authors.forename: Huck-Hui
authors.initials: HH
authors.lastname: Ng
mesh_terms: 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*
chemical_list: D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D000071317:Nanog Homeobox Protein; C475540:Nanog protein, mouse; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse