Activation of clustered IFNγ target genes drives cohesin-controlled transcriptional memory. Siwek et al
Cytokine activation of cells induces gene networks involved in inflammation and immunity. Transient gene activation can have a lasting impact even in the absence of ongoing transcription, known as long-term transcriptional memory. Here we explore the nature of the establishment and maintenance of IFNγ-induced priming of human cells. We find that while both 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 of enhanced innate immune signaling.