Fumeaux Coralie, Radhakrishnan Sunish Kumar, Ardissone Silvia, Théraulaz Laurence, Frandi Antonio, Martins Daniel, Nesper Jutta, Abel Sören, Jenal Urs, Viollier Patrick H
Department Microbiology and Molecular Medicine, Faculty of Medicine/CMU, Institute of Genetics and Genomics in Geneva (iGE3), University of Geneva, Rue Michel Servet 1, 1211 Genève 4, Switzerland.
1] Department Microbiology and Molecular Medicine, Faculty of Medicine/CMU, Institute of Genetics and Genomics in Geneva (iGE3), University of Geneva, Rue Michel Servet 1, 1211 Genève 4, Switzerland [2].
Nat Commun. 2014 Jun 18;5:4081. doi: 10.1038/ncomms5081.
Zinc-finger domain transcriptional regulators regulate a myriad of functions in eukaryotes. Interestingly, ancestral versions (MucR) from Alpha-proteobacteria control bacterial virulence/symbiosis. Whether virulence regulators can also control cell cycle transcription is unknown. Here we report that MucR proteins implement a hitherto elusive primordial S→G1 transcriptional switch. After charting G1-specific promoters in the cell cycle model Caulobacter crescentus by comparative ChIP-seq, we use one such promoter as genetic proxy to unearth two MucR paralogs, MucR1/2, as constituents of a quadripartite and homeostatic regulatory module directing the S→G1 transcriptional switch. Surprisingly, MucR orthologues that regulate virulence and symbiosis gene transcription in Brucella, Agrobacterium or Sinorhizobium support this S→G1 switch in Caulobacter. Pan-genomic ChIP-seq analyses in Sinorhizobium and Caulobacter show that this module indeed targets orthologous genes. We propose that MucR proteins and possibly other virulence regulators primarily control bacterial cell cycle (G1-phase) transcription, rendering expression of target (virulence) genes periodic and in tune with the cell cycle.
锌指结构域转录调节因子调控真核生物中的众多功能。有趣的是，来自α-变形菌的祖先版本（MucR）控制细菌的毒力/共生。毒力调节因子是否也能控制细胞周期转录尚不清楚。在此，我们报告MucR蛋白实现了一种迄今为止难以捉摸的原始S→G1转录开关。通过比较染色质免疫沉淀测序（ChIP-seq）在细胞周期模型新月柄杆菌中绘制G1特异性启动子后，我们使用其中一个这样的启动子作为遗传代理，发掘出两个MucR旁系同源物MucR1/2，它们是指导S→G1转录开关的四方稳态调节模块的组成部分。令人惊讶的是，在布鲁氏菌、根癌土壤杆菌或中华根瘤菌中调节毒力和共生基因转录的MucR直系同源物在新月柄杆菌中支持这种S→G1开关。在中华根瘤菌和新月柄杆菌中的泛基因组ChIP-seq分析表明，该模块确实靶向直系同源基因。我们提出，MucR蛋白以及可能的其他毒力调节因子主要控制细菌细胞周期（G1期）转录，使靶标（毒力）基因的表达具有周期性并与细胞周期同步。
