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Transient histone deacetylase inhibition induces cellular memory of gene expression and 3D genome folding.
Nat Genet, 58(2):404-417.
Epigenetic memory enables the propagation of gene expression patterns followingtransient stimuli. Although three-dimensional chromatin organization is emergingas a key regulator of genome function, it is unknown whether it contributes tocellular memory. Here we establish that acute perturbation of the epigenome caninduce cellular memory of gene expression in mouse embryonic stem cells. Weuncover how a pulse of histone deacetylase inhibition translates to changes intranscription, histone modifications and genome folding. While most epigenomicand transcriptional changes are initially reversed once the perturbation isremoved, some loci remain transcriptionally deregulated and genome architecturepartially maintains its perturbed conformation. Consequently, a second pulse oftransient hyperacetylation induces stronger memory of transcriptionalderegulation. Using ultradeep Micro-C, we associate memory of gene expressionwith repressive Polycomb-mediated chromatin topology. These results demonstratehow cells can record transient stresses in their genome architecture, therebyenabling an enhanced response to subsequent perturbations.
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