Kumar Santhust, Vendruscolo Michele, Singh Amit, Kumar Dhiraj, Samal Areejit
Department of Physics and Astrophysics, University of Delhi, Delhi, India.
Mol Biosyst. 2015 Mar;11(3):930-41. doi: 10.1039/c4mb00298a. Epub 2015 Jan 19.
The transcriptional regulation of gene expression is orchestrated by complex networks of interacting genes. Increasing evidence indicates that these 'transcriptional regulatory networks' (TRNs) in bacteria have an inherently hierarchical architecture, although the design principles and the specific advantages offered by this type of organization have not yet been fully elucidated. In this study, we focussed on the hierarchical structure of the TRN of the gram-positive bacterium Bacillus subtilis and performed a comparative analysis with the TRN of the gram-negative bacterium Escherichia coli. Using a graph-theoretic approach, we organized the transcription factors (TFs) and σ-factors in the TRNs of B. subtilis and E. coli into three hierarchical levels (Top, Middle and Bottom) and studied several structural and functional properties across them. In addition to many similarities, we found also specific differences, explaining the majority of them with variations in the distribution of σ-factors across the hierarchical levels in the two organisms. We then investigated the control of target metabolic genes by transcriptional regulators to characterize the differential regulation of three distinct metabolic subsystems (catabolism, anabolism and central energy metabolism). These results suggest that the hierarchical architecture that we observed in B. subtilis represents an effective organization of its TRN to achieve flexibility in response to a wide range of diverse stimuli.
基因表达的转录调控是由相互作用基因的复杂网络精心编排的。越来越多的证据表明，细菌中的这些“转录调控网络”（TRN）具有内在的层次结构，尽管这种组织类型的设计原则和具体优势尚未完全阐明。在本研究中，我们聚焦于革兰氏阳性菌枯草芽孢杆菌TRN的层次结构，并与革兰氏阴性菌大肠杆菌的TRN进行了比较分析。我们采用图论方法，将枯草芽孢杆菌和大肠杆菌TRN中的转录因子（TFs）和σ因子组织成三个层次水平（顶层、中层和底层），并研究了它们之间的几种结构和功能特性。除了许多相似之处外，我们还发现了特定的差异，并用两种生物体中σ因子在层次水平上分布的变化来解释其中的大部分差异。然后，我们研究了转录调节因子对目标代谢基因的控制，以表征三个不同代谢子系统（分解代谢、合成代谢和中心能量代谢）的差异调控。这些结果表明，我们在枯草芽孢杆菌中观察到的层次结构代表了其TRN的一种有效组织形式，以实现对广泛多样刺激的灵活响应。
