  Reconciling the stability of epigenetic patterns with the rapid turnover of
histone modifications and their adaptability to external stimuli is an
outstanding challenge. Here, we propose a new biophysical mechanism that can
establish and maintain robust yet plastic epigenetic domains via genomic
bookmarking (GBM). We model chromatin as a recolourable polymer whose segments
bear non-permanent histone marks (or colours) which can be modified by "writer"
proteins. The three-dimensional chromatin organisation is mediated by protein
bridges, or "readers", such as Polycomb Repressive Complexes and Transcription
Factors. The coupling between readers and writers drives spreading of
biochemical marks and sustains the memory of local chromatin states across
replication and mitosis. In contrast, GBM-targeted perturbations destabilise
the epigenetic patterns. Strikingly, we demonstrate that GBM alone can explain
the full distribution of Polycomb marks in a whole Drosophila chromosome. We
finally suggest that our model provides a starting point for an understanding
of the biophysics of cellular differentiation and reprogramming.
