Division of Theoretical Physics, Physics Department, Aristotle University of Thessaloniki, 54124, Thessaloniki, Greece.
PharmaInformatics Unit, Research Center ATHENA, Athens, Greece.
NPJ Syst Biol Appl. 2020 Feb 17;6(1):5. doi: 10.1038/s41540-020-0124-1.
For a long time it has been hypothesized that bacterial gene regulation involves an intricate interplay of the transcriptional regulatory network (TRN) and the spatial organization of genes in the chromosome. Here we explore this hypothesis both on a structural and on a functional level. On the structural level, we study the TRN as a spatially embedded network. On the functional level, we analyze gene expression patterns from a network perspective ("digital control"), as well as from the perspective of the spatial organization of the chromosome ("analog control"). Our structural analysis reveals the outstanding relevance of the symmetry axis defined by the origin (Ori) and terminus (Ter) of replication for the network embedding and, thus, suggests the co-evolution of two regulatory infrastructures, namely the transcriptional regulatory network and the spatial arrangement of genes on the chromosome, to optimize the cross-talk between two fundamental biological processes: genomic expression and replication. This observation is confirmed by the functional analysis based on the differential gene expression patterns of more than 4000 pairs of microarray and RNA-Seq datasets for E. coli from the Colombos Database using complex network and machine learning methods. This large-scale analysis supports the notion that two logically distinct types of genetic control are cooperating to regulate gene expression in a complementary manner. Moreover, we find that the position of the gene relative to the Ori is a feature of very high predictive value for gene expression, indicating that the Ori-Ter symmetry axis coordinates the action of distinct genetic control mechanisms.
长期以来，人们一直假设细菌基因调控涉及转录调控网络（TRN）和染色体中基因空间组织的复杂相互作用。在这里，我们从结构和功能两个层面来探索这一假设。在结构层面上，我们将 TRN 作为一个空间嵌入网络进行研究。在功能层面上，我们从网络角度（“数字控制”）以及从染色体空间组织的角度（“模拟控制”）分析基因表达模式。我们的结构分析揭示了复制起点（ori）和终点（ter）定义的对称轴对于网络嵌入的显著相关性，因此，这表明两个调节基础设施，即转录调控网络和染色体上基因的空间排列，共同进化以优化两个基本生物过程之间的交流：基因组表达和复制。基于哥伦比亚数据库中超过 4000 对微阵列和 RNA-Seq 数据集的差异基因表达模式，使用复杂网络和机器学习方法对大肠杆菌进行的功能分析证实了这一观察结果。这项大规模分析支持了这样一种观点，即两种逻辑上不同的遗传控制类型正在协同作用，以互补的方式调节基因表达。此外，我们发现基因相对于 ori 的位置是基因表达具有非常高预测价值的特征，这表明 ori-ter 对称轴协调了不同遗传控制机制的作用。
