Integration of external signaling pathways with the core transcriptional network in embryonic stem cells

被引:2240
作者
Chen, Xi [2 ,3 ]
Xu, Han
Yuan, Ping [2 ]
Fang, Fang [2 ,3 ]
Huss, Mikael
Vega, Vinsensius B.
Wong, Eleanor [1 ]
Orlov, Yuriy L. [4 ]
Zhang, Weiwei [2 ,3 ]
Jiang, Jianming [2 ,3 ]
Loh, Yuin-Han [2 ,3 ]
Yeo, Hock Chuan [4 ]
Yeo, Zhen Xuan [4 ]
Narang, Vipin
Govindarajan, Kunde Ramamoorthy
Leong, Bernard
Shahab, Atif
Ruan, Yijun [1 ]
Bourque, Guillaume
Sung, Wing-Kin
Clarke, Neil D. [4 ]
Wei, Chia-Lin [1 ]
Ng, Huck-Hui [2 ,3 ]
机构
[1] Genome Inst Singapore, Genome Technol & Biol Grp, Singapore 138672, Singapore
[2] Genome Inst Singapore, Gene Regulat Lab, Singapore 138672, Singapore
[3] Natl Univ Singapore, Dept Biol Sci, Singapore 117543, Singapore
[4] Genome Inst Singapore, Computat & Syst Biol Grp, Singapore 138672, Singapore
关键词
D O I
10.1016/j.cell.2008.04.043
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 [生物化学与分子生物学]; 081704 [应用化学];
摘要
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.
引用
收藏
页码:1106 / 1117
页数:12
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