Ekdahl Alyssa M, Turula Agata, Schroeder Jeremy W, Hurto Rebecca, Liu Quancheng, Freddolino Lydia, Contreras Lydia M
Mcketta Department of Chemical Engineering, University of Texas at Austin, Austin TX.
Department of Biological Chemistry and Department of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor MI.
bioRxiv. 2025 Aug 23:2025.08.23.671944. doi: 10.1101/2025.08.23.671944.
Recent studies have demonstrated the importance of dynamic heterochromatin-like regions in bacterial gene regulation, particularly for adaptation to changing environments. Here, we have measured the dynamic regulatory protein-DNA landscape of the tuberculosis vaccine strain, BCG Pasteur, under the pathogenically-relevant condition of iron starvation. Our results capture for the first time the overall protein occupancy landscape of the genome of BCG, identifying extended protein occupancy domains likely composed of diverse sets of nucleoid-associated proteins and transcription factors. Importantly, we find chromatin-directed regulation of stress-responsive genes like siderophores. Furthermore, through comparison with the free-living , we identified a specific class of extended protein occupancy domains that are associated with conserved genomic regions across the two organisms, whereas regions with low protein occupancy often lack conservation. Our findings thus comprehensively reveal the contributions of both local regulators and chromatin structure to gene regulation and evolution in mycobacteria.
最近的研究表明，动态异染色质样区域在细菌基因调控中具有重要作用，特别是在适应不断变化的环境方面。在此，我们测量了结核疫苗菌株卡介苗巴斯德株在与致病相关的铁饥饿条件下的动态调控蛋白 - DNA 图谱。我们的结果首次捕捉到了卡介苗基因组的整体蛋白占据图谱，确定了可能由多种类核相关蛋白和转录因子组成的扩展蛋白占据结构域。重要的是，我们发现了对铁载体等应激反应基因的染色质导向调控。此外，通过与自由生活菌进行比较，我们确定了一类特定的扩展蛋白占据结构域，它们与这两种生物体中保守的基因组区域相关，而蛋白占据率低的区域往往缺乏保守性。因此，我们的研究结果全面揭示了局部调节因子和染色质结构对分枝杆菌基因调控和进化的贡献。
