Paper alert: Transient histone deacetylase inhibition induces cellular memory of gene expression and 3D genome folding!

Although three-dimensional chromatin organization is emerging as a key regulator of genome function, it is unknown whether it contributes to cellular memory. Here we show that acute perturbation of the epigenome induces cellular memory of gene expression in mouse ESCs, where a transient inhibition of histone deacetylase drives transcriptional changes, histone modifications and genome folding. While most transcriptional and epigenomic changes are initially reversed after the perturbation, some loci remain transcriptionally active and their genome architecture is irreversibly perturbed. Moreover, a second pulse of transient hyperacetylation furhter increases these long-term transcriptional defects. Interestingly, micro-C results and functional experiments indicate that this memory of gene expression is associated with repressive Polycomb-mediated chromatin topology, demonstraging how cells can record transient stresses in their genome architecture to enable an enhanced response to later perturbations.