Abstract

Every cell remembers who it is, e.g., a neuron or a skin cell. This cellular identity is maintained to a great extent by epigenetic memory, patterns of chemical modifications of DNA and histones along the genome. We ask how cells can maintain the epigenetic memory for hundreds of generations. We modeled joint dynamics of chromosomes and histone marks: loss and spreading of marks, and refolding of chromosomes through the cell cycle. A surprising analogy between the spreading of histone marks and the spreading of a pandemic helped to identify factors that provide robust memory. We further found a parallel between epigenetic memory and an associative memory in the neural network. Our analysis shows that operation of chromatin as an epigenetic memory device requires folding of the marked region into the dense and spatial segregated condensate, enzyme limitation, and spatial spreading of the marks. Our findings suggest a functional role for the phase-separated genome.