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. 2008 Jun 13;133(6):1106-17.
doi: 10.1016/j.cell.2008.04.043.

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

Xi Chen  1 , Han Xu, Ping Yuan, Fang Fang, Mikael Huss, Vinsensius B Vega, Eleanor Wong, Yuriy L Orlov, Weiwei Zhang, Jianming Jiang, Yuin-Han Loh, Hock Chuan Yeo, Zhen Xuan Yeo, Vipin Narang, Kunde Ramamoorthy Govindarajan, Bernard Leong, Atif Shahab, Yijun Ruan, Guillaume Bourque, Wing-Kin Sung, Neil D Clarke, Chia-Lin Wei, Huck-Hui Ng
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Free article

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

Xi Chen et al. Cell. .
Free article

Abstract

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.

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