Network-dosage compensation topologies as recurrent network motifs in natural gene networks.
Network-dosage compensation topologies as recurrent network motifs in natural gene networks.
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DOI：
10.1186/1752-0509-8-69
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发表时间：
2014-06-14
影响因子：
--
通讯作者：
Acar M
中科院分区：
文献类型：
--
作者：
Song R;Liu P;Acar M
基因表达的全球噪声和细胞周期进程中的染色体复制不可避免地导致细胞中基因网络的有效拷贝数的波动。网络拷贝数的这些间接和直接改变有可能改变基因网络的产量或活性。对于其特定活动水平对于最佳地维持细胞功能至关重要的网络，细胞需要实施机制来强有力地补偿网络剂量波动的影响。在这里，我们确定了广义N组分基因网络是网络剂量补偿的必要条件，并证明了补偿机制可以在大范围的基因表达水平上稳健地运行。此外，我们还证明了网络剂量补偿的必要条件也是充分的。最后，利用全基因组蛋白质-DNA和蛋白质-蛋白质相互作用数据，我们在酵母基因组中搜索特定剂量补偿基序的丰度，并表明相当大比例的自然网络至少包含一个剂量补偿基序。我们的结果支持了这样的假设，即网络剂量补偿所必需的特殊网络拓扑可能是真核基因组中的递归网络基序，因此可能是细胞中基因网络组装的重要设计原则。
Global noise in gene expression and chromosome duplication during cell-cycle progression cause inevitable fluctuations in the effective number of copies of gene networks in cells. These indirect and direct alterations of network copy numbers have the potential to change the output or activity of a gene network. For networks whose specific activity levels are crucial for optimally maintaining cellular functions, cells need to implement mechanisms to robustly compensate the effects of network dosage fluctuations. Here, we determine the necessary conditions for generalized N-component gene networks to be network-dosage compensated and show that the compensation mechanism can robustly operate over large ranges of gene expression levels. Furthermore, we show that the conditions that are necessary for network-dosage compensation are also sufficient. Finally, using genome-wide protein-DNA and protein-protein interaction data, we search the yeast genome for the abundance of specific dosage-compensation motifs and show that a substantial percentage of the natural networks identified contain at least one dosage-compensation motif. Our results strengthen the hypothesis that the special network topologies that are necessary for network-dosage compensation may be recurrent network motifs in eukaryotic genomes and therefore may be an important design principle in gene network assembly in cells.
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