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.

中文翻译：

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染色体复制起点在逻辑上协调细菌遗传调控的不同类型。

长期以来，人们一直认为细菌基因调控涉及转录调控网络（TRN）和染色体中基因的空间组织的复杂相互作用。在这里，我们在结构和功能层面上都探讨了这一假设。在结构级别上，我们将TRN研究为空间嵌入式网络。在功能级别上，我们从网络角度（“数字控制”）以及从染色体的空间组织角度（“模拟控制”）分析基因表达模式。我们的结构分析揭示了对称轴的出色相关性，该对称轴由网络的复制起点（Ori）和终点（Ter）定义，因此建议两个监管基础结构共同演进，即转录调控网络和染色体上基因的空间排列，以优化两个基本生物学过程之间的串扰：基因组表达和复制。通过基于复杂网络和机器学习方法的科伦坡斯数据库中4000多对微阵列和大肠杆菌RNA-Seq数据集的差异基因表达模式进行的功能分析，证实了该观察结果。这种大规模的分析支持以下观点：两种逻辑上不同的基因控制正在以互补的方式协同调节基因表达。此外，我们发现该基因相对于Ori的位置对于基因表达具有很高的预测价值，