Cytokine activation of cells induces gene networks involved in inflammation and immunity. Transient gene activation can have a lasting effect even in the absence of ongoing transcription, known as long-term transcriptional memory. Here we explore the nature of the establishment and maintenance of interferon γ (IFNγ)-induced priming of human cells. We find that, although ongoing transcription and local chromatin signatures are short-lived, the IFNγ-primed state stably propagates through at least 14 cell division cycles. Single-cell analysis reveals that memory is manifested by an increased probability of primed cells to engage in target gene expression, correlating with the strength of initial gene activation. Further, we find that strongly memorized genes tend to reside in genomic clusters and that long-term memory of these genes is locally restricted by cohesin. We define the duration, stochastic nature, and molecular mechanisms of IFNγ-induced transcriptional memory, relevant to understanding enhanced innate immune signaling.

细胞的细胞因子激活诱导涉及炎症和免疫力的基因网络。即使没有正在进行的转录（称为长期转录记忆），瞬时基因激活也可能具有持久作用。在这里，我们探索干扰素γ（IFNγ）诱导的人类细胞启动和建立的本质。我们发现，尽管正在进行的转录和局部染色质签名是短暂的，但IFNγ引发的状态稳定地传播了至少14个细胞分裂周期。单细胞分析揭示记忆是由引发细胞参与靶基因表达的可能性增加而体现的，这与初始基因激活的强度有关。进一步，我们发现强烈记忆的基因倾向于驻留在基因组簇中，而这些基因的长期记忆受到粘着蛋白的局部限制。我们定义了IFNγ诱导的转录记忆的持续时间，随机性质和分子机制，与了解增强的先天免疫信号有关。