Although several studies have provided important insights into the general principles of biological networks, the link between network organization and the genome-scale dynamics of the underlying entities (genes, mRNAs, and proteins) and its role in systems behavior remain unclear. Here we show that transcription factor (TF) dynamics and regulatory network organization are tightly linked. By classifying TFs in the yeast regulatory network into three hierarchical layers (top, core, and bottom) and integrating diverse genome-scale datasets, we find that the TFs have static and dynamic properties that are similar within a layer and different across layers. At the protein level, the top-layer TFs are relatively abundant, long-lived, and noisy compared with the core- and bottom-layer TFs. Although variability in expression of top-layer TFs might confer a selective advantage, as this permits at least some members in a clonal cell population to initiate a response to changing conditions, tight regulation of the core- and bottom-layer TFs may minimize noise propagation and ensure fidelity in regulation. We propose that the interplay between network organization and TF dynamics could permit differential utilization of the same underlying network by distinct members of a clonal cell population.

中文翻译：

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基因组分析揭示了转录因子动力学和调节网络结构之间的紧密联系。

尽管几项研究提供了对生物网络一般原理的重要见解，但网络组织与潜在实体（基因、mRNA 和蛋白质）的基因组规模动态之间的联系及其在系统行为中的作用仍不清楚。在这里，我们表明转录因子 (TF) 动力学和调节网络组织紧密相连。通过将酵母调控网络中的 TF 分为三个层次层（顶部、核心和底部）并整合不同的基因组规模数据集，我们发现 TF 具有静态和动态特性，这些特性在一个层内相似而在层间不同。在蛋白质水平上，与核心层和底层 TF 相比，顶层 TF 相对丰富、寿命长且噪音大。尽管顶层 TF 表达的可变性可能会带来选择性优势，因为这至少允许克隆细胞群中的某些成员对不断变化的条件做出反应，但对核心和底层 TF 的严格调控可以最大限度地减少噪声传播并确保监管的保真度。我们建议网络组织和 TF 动力学之间的相互作用可以允许克隆细胞群的不同成员对相同底层网络的不同利用。