Université de Paris, Laboratoire Matière et Systèmes Complexes, CNRS UMR 7057, F-75013 Paris, France.
Université de Paris, Laboratoire Génomes, Biologie Cellulaire et Thérapeutiques, CNRS UMR7212, INSERM U944, Centre de Recherche St Louis, F- 75010 Paris, France.
Cells. 2019 Jun 13;8(6):582. doi: 10.3390/cells8060582.
Cellular memory is a critical ability that allows microorganisms to adapt to potentially detrimental environmental fluctuations. In the unicellular eukaryote , cellular memory can take the form of faster or slower responses within the cell population to repeated stresses. Using microfluidics and fluorescence time-lapse microscopy, we studied how yeast responds to short, pulsed hyperosmotic stresses at the single-cell level by analyzing the dynamic behavior of the stress-responsive promoter (pSTL1) fused to a fluorescent reporter. We established that pSTL1 exhibits variable successive activation patterns following two repeated short stresses. Despite this variability, most cells exhibited a memory of the first stress as decreased pSTL1 activity in response to the second stress. Notably, we showed that genomic location is important for the memory effect, since displacement of the promoter to a pericentromeric chromatin domain decreased the transcriptional strength of pSTL1 and led to a loss of memory. This study provides a quantitative description of a cellular memory that includes single-cell variability and highlights the contribution of chromatin structure to stress memory.
细胞记忆是一种关键能力，使微生物能够适应潜在的有害环境波动。在单细胞真核生物中，细胞记忆可以表现为细胞群体对重复应激的更快或更慢的反应。我们使用微流控技术和荧光延时显微镜，通过分析与荧光报告基因融合的应激响应启动子 (pSTL1) 的动态行为，在单细胞水平上研究了酵母如何对短期、脉冲高渗应激做出反应。我们发现，pSTL1 在两次重复的短期应激后表现出可变的连续激活模式。尽管存在这种可变性，但大多数细胞在第二次应激时表现出对第一次应激的记忆，即 pSTL1 活性降低。值得注意的是，我们表明基因组位置对于记忆效应很重要，因为将启动子转移到着丝粒周围染色质区域会降低 pSTL1 的转录强度，并导致记忆丧失。这项研究提供了对包括单细胞变异性在内的细胞记忆的定量描述，并强调了染色质结构对应激记忆的贡献。
