Shaping Epigenetic Memory via Genomic Bookmarking

Davide Michieletto, Michael Chiang, Davide Coli, Argyris Papantonis, Enzo Orlandini, Peter R. Cook, Davide Marenduzzo

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.
Original languageEnglish
Pages (from-to)83-93
JournalNucleic Acids Research
Volume46
Issue number1
DOIs
Publication statusPublished - 28 Nov 2017

Keywords / Materials (for Non-textual outputs)

  • q-bio.SC
  • cond-mat.soft
  • physics.bio-ph

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