2017/09/30 by Davide Michieletto, Michael Chiang, Davide Coli +6 · 1 citation
Agricultural and Biological Sciences · Biochemistry, Genetics and Molecular Biology · Physics and Astronomy · #Bivalent chromatin #Bookmarking #Chromatin #Chromatin remodeling #Chromosomal and Genetic Variations #Epigenesis #Epigenetics #Epigenetics and DNA Methylation #Genomics and Chromatin Dynamics #Histone #Histone code #cond-mat.soft #physics.bio-ph #q-bio.SC
paper · pdf · doi:10.1093/nar/gkx1200
published as Nucleic Acids Res. (2017) · 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
openalex created_date 2017/09/15 · openalex publication_date 2017/11/19 · arxiv created 2017/11/28 · arxiv updated 2017/11/29 · openalex updated_date 2026/08/05
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.