Shaping Epigenetic Memory via Genomic Bookmarking

Abstract

Reconciling the stability of epigenetic landscapes 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 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. On the contrary, GBM-targeted perturbations destabilise the epigenetic landscape. Strikingly, we show that GBM can explain the full distribution of Polycomb marks in a whole Drosophila chromosome. Our model provides a starting point for an understanding of the biophysics of cellular differentiation and reprogramming.