胚胎干细胞中外部信号通路与核心转录网络的整合。

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

作者信息

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

机构信息

Gene Regulation Laboratory, Genome Institute of Singapore, Singapore 138672.

出版信息

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

DOI:10.1016/j.cell.2008.04.043

PMID:18555785

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.

摘要

转录因子（TFs）及其与靶标的特定相互作用对于确定基因表达程序至关重要。为了深入了解胚胎干细胞（ES细胞）中的转录调控网络，我们使用染色质免疫沉淀结合超高通量DNA测序（ChIP-seq）来绘制13种序列特异性TFs（Nanog、Oct4、STAT3、Smad1、Sox2、Zfx、c-Myc、n-Myc、Klf4、Esrrb、Tcfcp2l1、E2f1和CTCF）以及2种转录调节因子（p300和Suz12）的结合位点。已知这些因子作为LIF和BMP信号通路的组成部分、自我更新调节因子以及关键重编程因子，在ES细胞生物学中发挥着不同作用。我们的研究为信号通路整合到ES细胞特异性转录调控网络中提供了见解。有趣的是，我们发现了不同TFs广泛靶向的特定基因组区域。总体而言，TF结合位点的全面图谱确定了定义ES细胞特性的转录调控网络的重要特征。