Martínez-Antonio Agustino, Janga Sarath Chandra, Thieffry Denis
Departamento de Ingeniería Genética, Centro de Investigación y de Estudios Avanzados, Instituto Politécnico Nacional, Campus Guanajuato, Irapuato 36500, México.
J Mol Biol. 2008 Aug 1;381(1):238-47. doi: 10.1016/j.jmb.2008.05.054. Epub 2008 May 29.
Taking advantage of available functional data associated with 115 transcription and 7 sigma factors, we have performed a structural analysis of the regulatory network of Escherichia coli. While the mode of regulatory interaction between transcription factors (TFs) is predominantly positive, TFs are frequently negatively autoregulated. Furthermore, feedback loops, regulatory motifs and regulatory pathways are unevenly distributed in this network. Short pathways, multiple feed-forward loops and negative autoregulatory interactions are particularly predominant in the subnetwork controlling metabolic functions such as the use of alternative carbon sources. In contrast, long hierarchical cascades and positive autoregulatory loops are overrepresented in the subnetworks controlling developmental processes for biofilm and chemotaxis. We propose that these long transcriptional cascades coupled with regulatory switches (positive loops) for external sensing enable the coexistence of multiple bacterial phenotypes. In contrast, short regulatory pathways and negative autoregulatory loops enable an efficient homeostatic control of crucial metabolites despite external variations. TFs at the core of the network coordinate the most basic endogenous processes by passing information onto multi-element circuits. Transcriptional expression data support broader and higher transcription of global TFs compared to specific ones. Global regulators are also more broadly conserved than specific regulators in bacteria, pointing to varying functional constraints.
利用与115个转录因子和7个σ因子相关的现有功能数据，我们对大肠杆菌的调控网络进行了结构分析。虽然转录因子（TFs）之间的调控相互作用模式主要为正向，但TFs经常受到负向自调控。此外，反馈回路、调控基序和调控途径在该网络中分布不均。短途径、多个前馈回路和负向自调控相互作用在控制代谢功能（如利用替代碳源）的子网络中尤为突出。相比之下，长层次级联和正向自调控回路在控制生物膜和趋化性发育过程的子网络中占比过高。我们提出，这些长转录级联与用于外部感知的调控开关（正向回路）相结合，使得多种细菌表型得以共存。相比之下，短调控途径和负向自调控回路能够在外部变化的情况下对关键代谢物进行有效的稳态控制。网络核心的TFs通过将信息传递到多元素回路来协调最基本的内源性过程。转录表达数据表明，与特定TFs相比，全局TFs的转录范围更广、水平更高。全局调节因子在细菌中也比特定调节因子具有更广泛的保守性，这表明存在不同的功能限制。
