Centromeres, a highly conserved locus of eukaryotic chromosomes, have critical function for genome stability and integrity. Because their centromeric DNA sequences are necessary and sufficient for kinetochore recruitment and DNA segregation, point centromeres of Saccharomyces cerevisiae chromosomes provide an attractive system for the study of the regulation of centromere function. Using the mathematical model of Boolean gene regulatory networks, the gene regulatory dynamics of centromere region of S. cerevisiae (budding yeast), which is actively involved in the cell-cycle, has been examined. A gene regulatory network containing the relevant centromere genes of the model organism from biological databases was established and all possible cellular phenotypes subjected to a synchronous gene regulation and attracted to several basins. Gene expression in the largest attractor was compared with the biological data by obtaining changes in the cell-cycle. We show that the model for centromere function recovers a single cyclic attractor. The trajectory flow diagram plotted over all initial conditions of the system also shows good correspondence with the cell-cycle phases. Although other upstream signals are possibly involved in the regulation of centromere genes, proposed interactions with selected cell-cycle genes were sufficient to recover whole cell-cycle process. To truly clarify these proposed regulatory interactions of candidate genes for centromere function, profiling and analyzing their expression levels over time with expanded nodes/edges are required. Moreover, a previously modeled gene knock-down mechanism applied to the network and robustness versus knock-down was interpreted based on the obtained consequences.

中文翻译：

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酿酒酵母着丝粒功能的布尔基因调控网络模型

着丝粒是真核染色体的一个高度保守的基因座，对基因组的稳定性和完整性具有关键作用。因为它们的着丝粒 DNA 序列对于着丝粒募集和 DNA 分离是必要和充分的，酿酒酵母染色体的点着丝粒为研究着丝粒功能的调节提供了一个有吸引力的系统。使用布尔基因调控网络的数学模型，研究了积极参与细胞周期的酿酒酵母（芽殖酵母）着丝粒区域的基因调控动力学。建立了包含来自生物数据库的模式生物的相关着丝粒基因的基因调控网络，所有可能的细胞表型都受到同步基因调控并被吸引到几个盆地。通过获得细胞周期的变化，将最大吸引子中的基因表达与生物学数据进行比较。我们表明着丝粒功能模型恢复了单个循环吸引子。在系统的所有初始条件下绘制的轨迹流程图也显示出与细胞周期阶段的良好对应。尽管其他上游信号可能参与着丝粒基因的调控，但与选定细胞周期基因的相互作用足以恢复整个细胞周期过程。为了真正阐明这些拟定的着丝粒功能候选基因的调节相互作用，需要使用扩展的节点/边缘来分析和分析它们随时间的表达水平。而且，