众多序列特异的转录因子 (transcription factors ,TFs) 组合而成交叉的调控网络,这些调控网络构成细胞发挥生物学功能的基础。
9月5日,国际著名杂志Cell在线发表了美国华盛顿大学等科研人员的一篇题为Circuitry and Dynamics of Human Transcription Factor Regulatory Networks的研究论文,报道了人转录因子调控网络环路,动力学和组织原理。
研究人员采用全基因的体内DNaseI 足迹法,在41种不同的细胞和组织中找到了475个序列特异的转录因子间的联系 ,然后分析这些联系的动力学。
研究发现人转录因子网络具有高度的细胞选择性,细胞选择性由数种因子驱动,其中包括在控制细胞身份中未被识别的调节子。而且,还鉴定出多种影响转录调控网络的广泛表达的因子。
令人震惊的是,尽管转录因子内在的多样性,所有细胞类型的调控网络各自独立地汇聚到一起,如同生命体的神经网络。
本研究提供了人转录因子调控网络环路,动力学和组织原理等的广泛描述。(生物谷Bioon.com)
doi:10.1016/j.cell.2012.04.040
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Circuitry and Dynamics of Human Transcription Factor Regulatory Networks
Shane Neph, Andrew B. Stergachis, Alex Reynolds, Richard Sandstrom, Elhanan Borenstein, John A. Stamatoyannopoulos
The combinatorial cross-regulation of hundreds of sequence-specific transcription factors (TFs) defines a regulatory network that underlies cellular identity and function. Here we use genome-wide maps of in vivo DNaseI footprints to assemble an extensive core human regulatory network comprising connections among 475 sequence-specific TFs and to analyze the dynamics of these connections across 41 diverse cell and tissue types. We find that human TF networks are highly cell selective and are driven by cohorts of factors that include regulators with previously unrecognized roles in control of cellular identity. Moreover, we identify many widely expressed factors that impact transcriptional regulatory networks in a cell-selective manner. Strikingly, in spite of their inherent diversity, all cell-type regulatory networks independently converge on a common architecture that closely resembles the topology of living neuronal networks. Together, our results provide an extensive description of the circuitry, dynamics, and organizing principles of the human TF regulatory network.