de Barsy Marie, Frandi Antonio, Panis Gaël, Théraulaz Laurence, Pillonel Trestan, Greub Gilbert, Viollier Patrick H
Institute of Microbiology, University Hospital Center, University of Lausanne, Lausanne, Switzerland.
Department of Microbiology and Molecular Medicine, Institute of Genetics and Genomics in Geneva (iGE3), Faculty of Medicine, University of Geneva, Geneva, Switzerland.
ISME J. 2016 Sep;10(9):2129-44. doi: 10.1038/ismej.2016.23. Epub 2016 Mar 8.
Like other obligate intracellular bacteria, the Chlamydiae feature a compact regulatory genome that remains uncharted owing to poor genetic tractability. Exploiting the reduced number of transcription factors (TFs) encoded in the chlamydial (pan-)genome as a model for TF control supporting the intracellular lifestyle, we determined the conserved landscape of TF specificities by ChIP-Seq (chromatin immunoprecipitation-sequencing) in the chlamydial pathogen Waddlia chondrophila. Among 10 conserved TFs, Euo emerged as a master TF targeting >100 promoters through conserved residues in a DNA excisionase-like winged helix-turn-helix-like (wHTH) fold. Minimal target (Euo) boxes were found in conserved developmentally-regulated genes governing vertical genome transmission (cytokinesis and DNA replication) and genome plasticity (transposases). Our ChIP-Seq analysis with intracellular bacteria not only reveals that global TF regulation is maintained in the reduced regulatory genomes of Chlamydiae, but also predicts that master TFs interpret genomic information in the obligate intracellular α-proteobacteria, including the rickettsiae, from which modern day mitochondria evolved.
与其他专性细胞内细菌一样,衣原体具有紧凑的调控基因组,但由于遗传易处理性较差,该基因组仍未被完全了解。利用衣原体(泛)基因组中编码的转录因子(TF)数量减少这一特点,将其作为支持细胞内生活方式的TF控制模型,我们通过染色质免疫沉淀测序(ChIP-Seq)确定了衣原体病原体嗜软骨瓦德西菌中TF特异性的保守图谱。在10个保守的TF中,Euo作为主要TF出现,通过类似DNA切除酶的翼状螺旋-转角-螺旋样(wHTH)结构域中的保守残基靶向100多个启动子。在控制垂直基因组传递(胞质分裂和DNA复制)和基因组可塑性(转座酶)的保守发育调控基因中发现了最小靶标(Euo)框。我们对细胞内细菌的ChIP-Seq分析不仅揭示了衣原体简化调控基因组中全局TF调控得以维持,还预测主要TF在专性细胞内α-变形菌中解释基因组信息,包括立克次氏体,现代线粒体就是从立克次氏体进化而来的。