Circuitry and dynamics of human transcription factor regulatory networks.

Circuitry and dynamics of human transcription factor regulatory networks.
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DOI:
10.1016/j.cell.2012.04.040
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发表时间:
2012-09-14
期刊:
影响因子:
64.5
通讯作者:
Stamatoyannopoulos JA
Stamatoyannopoulos JA
中科院分区:
生物学1区
文献类型:
--
作者:
Neph S;Stergachis AB;Reynolds A;Sandstrom R;Borenstein E;Stamatoyannopoulos JA

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数百个序列特异性转录因子的组合交叉调节定义了构成细胞身份和功能基础的调节网络。在这里,我们使用体内DNaseI足迹的全基因组图谱来组装一个广泛的核心人类调控网络,该网络包括475个序列特异性转录因子之间的连接,并分析这些连接在41种不同细胞和组织类型中的动态。我们发现,人类转录因子网络是高度细胞选择性的,并由包括以前未被识别的作用,在控制细胞身份的调节因子的队列驱动。此外,我们确定了许多广泛表达的因素,影响转录调控网络的细胞选择性的方式。引人注目的是,尽管它们固有的多样性,所有细胞类型的调控网络独立地收敛于一个共同的架构,非常类似于活的神经元网络的拓扑结构。总之,我们的研究结果提供了人类转录因子调控网络的电路,动力学和组织原则的第一个描述。
The combinatorial cross-regulation of hundreds of sequence-specific transcription factors 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 transcription factors, and to analyze the dynamics of these connections across 41 diverse cell and tissue types. We find that human transcription factor 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 the first description of the circuitry, dynamics, and organizing principles of the human transcription factor regulatory network.
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