Nature：Rv0081基因可能是肺结核病原体适应组织缺氧长期生存的机制

肺结核是一种特别能使人身体虚弱的病，部分原因是“结核分枝杆菌”病原体能够无症状地在宿主体内长久存在很多个月、甚至几十年时间。对超过45个“结核分枝杆菌”转录因子所做的一项ChIP-Seq基因组图谱分析，结合来自这些因子的系统性过度表达的表达数据，被用来在系统范围内重建决定分支杆菌耐久力的调控网络。该网络揭示了对组织缺氧的适应与脂质代谢（二者都被认为是肺结核发病的关键）之间的联系，同时这项研究还发现以前未被研究过的转录因子Rv0081是该网络的一个调控枢纽。

英文摘要：

Nature   doi:10.1038/nature12337

The Mycobacterium tuberculosis regulatory network and hypoxia

James E. Galagan,Kyle Minch,Matthew Peterson,Anna Lyubetskaya,Elham Azizi,Linsday Sweet,Antonio Gomes,Tige Rustad,Gregory Dolganov,Irina Glotova,  Thomas Abeel, Chris Mahwinney,Adam D. Kennedy,  René Allard,William Brabant, Andrew Krueger,Suma Jaini,Brent Honda,Wen-Han Yu,Mark J. Hickey,  Jeremy Zucker,Christopher Garay,Brian Weiner,Peter Sisk,Christian Stolte et al.

We have taken the first steps towards a complete reconstruction of the Mycobacterium tuberculosis regulatory network based on ChIP-Seq and combined this reconstruction with system-wide profiling of messenger RNAs, proteins, metabolites and lipids during hypoxia and re-aeration. Adaptations to hypoxia are thought to have a prominent role in M. tuberculosis pathogenesis. Using ChIP-Seq combined with expression data from the induction of the same factors, we have reconstructed a draft regulatory network based on 50 transcription factors. This network model revealed a direct interconnection between the hypoxic response, lipid catabolism, lipid anabolism and the production of cell wall lipids. As a validation of this model, in response to oxygen availability we observe substantial alterations in lipid content and changes in gene expression and metabolites in corresponding metabolic pathways. The regulatory network reveals transcription factors underlying these changes, allows us to computationally predict expression changes, and indicates that Rv0081 is a regulatory hub.