Shaping Epigenetic Memory via Genomic Bookmarking

Abstract

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.

Published in Nucleic Acids Research; Supplementary Movies can be found at this url: https://www2.ph.ed.ac.uk/~dmichiel/ShapingEpigeneticMemory.html or https://www.youtube.com/watch?v=xY-DNP58yBU

References in corpus (4)

• Ephemeral protein binding to DNA shapes stable nuclear bodies and chromatin domains
• Theory for stability and regulation of epigenetic landscapes
• Epigenetic Transitions and Knotted Solitons in Stretched Chromatin
• A Polymer Model with Epigenetic Recolouring Reveals a Pathway for the de novo Establishment and 3D Organisation of Chromatin Domains

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• Chromatin state switching in a polymer model with mark-conformation coupling
• Competition between local erasure and long-range spreading of a single biochemical mark leads to epigenetic bistability
• A nonequilibrium strategy for fast target search on the genome
• Emergence of compact-disordered phase in a polymer Potts model