Topological and causal structure of the yeast transcriptional regulatory network
Topological and causal structure of the yeast transcriptional regulatory network
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DOI：
10.1038/ng873
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发表时间：
2002-05-01
期刊：
影响因子：
30.8
通讯作者：
Képès, F
中科院分区：
文献类型：
--
作者：
Guelzim, N;Bottani, S;Képès, F
对高通量生物数据的解释需要了解支持细胞功能的网络的设计原理。尤其重要的是遗传网络，这是一组通过直接转录调控相互作用的基因。发挥调节作用的基因编码专门的转录因子(以下称为调节蛋白)，这些转录因子可以结合受调控基因的特定DNA控制区来激活或抑制其转录。受调控的基因本身可能会以一种调控的方式发挥作用，在这种情况下，它们参与了一条因果途径。环路形成反馈电路。因为一个基因可以有几个连接，所以电路和通路可能会交叉连接，从而代表连接的组成部分。我们已经创建了一个图表，其中包括491个酵母基因之间通过遗传或生物化学方法建立的909个相互作用。每个被调控基因的调控蛋白数量呈指数衰减的窄分布。每种调控蛋白的调控基因数量具有更广泛的分布，其衰变规律类似于幂定律。假设在计算机生成的图表中，基因连接满足这些分布，但在其他方面是随机的，连接的局部聚集和短路反馈电路的数量在很大程度上被低估了。这种对随机性的偏离可能反映了功能限制，包括生物合成成本、反应延迟以及差异性和动态平衡调节。
Interpretation of high-throughput biological data requires a knowledge of the design principles underlying the networks that sustain cellular functions. Of particular importance is the genetic network, a set of genes that interact through directed transcriptional regulation. Genes that exert a regulatory role encode dedicated transcription factors (hereafter referred to as regulating proteins) that can bind to specific DNA control regions of regulated genes to activate or inhibit their transcription. Regulated genes may themselves act in a regulatory manner, in which case they participate in a causal pathway. Looping pathways form feedback circuits. Because a gene can have several connections, circuits and pathways may crosslink and thus represent connected components. We have created a graph of 909 genetically or biochemically established interactions among 491 yeast genes. The number of regulating proteins per regulated gene has a narrow distribution with an exponential decay. The number of regulated genes per regulating protein has a broader distribution with a decay resembling a power law. Assuming in computer-generated graphs that gene connections fulfill these distributions but are otherwise random, the local clustering of connections and the number of short feedback circuits are largely underestimated. This deviation from randomness probably reflects functional constraints that include biosynthetic cost, response delay and differentiative and homeostatic regulation.