Ekdahl Alyssa M, Julien Tatiana, Suraj Sahana, Kribelbauer-Swietek Judith F, Tavazoie Saeed, Freddolino Lydia, Contreras Lydia M
McKetta Department of Chemical Engineering, University of Texas at Austin, Austin, TX 78712, United States.
Department of Molecular Biosciences, University of Texas at Austin, Austin, TX 78712, United States.
Nucleic Acids Res. 2025 Jul 8;53(13). doi: 10.1093/nar/gkaf647.
Recent research has indicated the presence of highly protein occupied, transcriptionally silent regions of bacterial genomes which show functional parallels to eukaryotic heterochromatin. We utilized an integrative approach to track chromatin structure and transcription in Escherichia coli K-12 across a wide range of nutrient conditions. In the process, we identified multiple loci which act similarly to facultative heterochromatin in eukaryotes, normally silenced but permitting expression of genes under specific conditions. We also found a strong enrichment of small regulatory RNAs (sRNAs) among the set of differentially expressed transcripts during nutrient stress. Using a newly developed bioinformatic pipeline, the transcription factors (TFs) regulating sRNA expression were bioinformatically predicted, with experimental follow-up revealing novel relationships for 45 sRNA-TF candidates. Direct regulation of sRNA expression was confirmed by mutational analysis for five sRNAs of metabolic interest: IsrB (also known as AzuCR), CsrB and CsrC, GcvB, and GadY. Our integrative analysis thus reveals additional layers of complexity in the nutrient stress response in E. coli and provides a framework for revealing similar poorly understood regulatory logic in other organisms.
最近的研究表明，细菌基因组中存在高度蛋白质占据的转录沉默区域，这些区域在功能上与真核异染色质相似。我们采用综合方法，在广泛的营养条件下追踪大肠杆菌K-12中的染色质结构和转录情况。在此过程中，我们鉴定出多个位点，其作用类似于真核生物中的兼性异染色质，通常处于沉默状态，但在特定条件下允许基因表达。我们还发现，在营养应激期间差异表达的转录本中，小调节RNA（sRNA）大量富集。使用新开发的生物信息学流程，通过生物信息学预测了调控sRNA表达的转录因子（TF），实验后续揭示了45个sRNA-TF候选物的新关系。通过对5个具有代谢意义的sRNA进行突变分析，证实了对sRNA表达的直接调控：IsrB（也称为AzuCR）、CsrB和CsrC、GcvB以及GadY。因此，我们的综合分析揭示了大肠杆菌营养应激反应中额外的复杂层面，并为揭示其他生物体中类似的、理解不足的调控逻辑提供了一个框架。
