Gene-specific transcriptional memory in mammalian cell lineages

Phenotypically identical mammalian cells often display considerable variability in transcript levels of individual genes. How transcriptional activity propagates in cell lineages, and how this varies across genes is poorly understood. Here we combined live-cell imaging of short-lived transcriptional reporters in mouse embryonic stem cells with mathematical modelling to quantify the propagation of transcriptional activity over time and across cell generations. In sister cells we found mean transcriptional activity to be strongly correlated and transcriptional dynamics tended to be synchronous; both features control how quickly sister cells diverge in a gene-specific manner. Mean transcriptional activity was also highly correlated between mother and daughter cells, leading to multi-generational transcriptional memory whose duration scaled with the spread of transcriptional activities in the population. The resulting family-specific transcriptional levels suggest a potential role of transcriptional memory in patterning tissue gene expression.