Polymer model with Epigenetic Recoloring Reveals a Pathway for the de novo Establishment and 3D Organization of Chromatin Domains

D. Michieletto*, E. Orlandini, D. Marenduzzo

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

One of the most important problems in development is how epigenetic domains can first be established, and then maintained, within cells. To address this question, we propose a framework that couples three-dimensional chromatin folding dynamics to a “recoloring” process modeling the writing of epigenetic marks. Because many intrachromatin interactions are mediated by bridging proteins, we consider a “two-state” model with self-attractive interactions between two epigenetic marks that are alike (either active or inactive). This model displays a first-order-like transition between a swollen, epigenetically disordered phase and a compact, epigenetically coherent chromatin globule. If the self-attraction strength exceeds a threshold, the chromatin dynamics becomes glassy, and the corresponding interaction network freezes. By modifying the epigenetic read-write process according to more biologically inspired assumptions, our polymer model with recoloring recapitulates the ultrasensitive response of epigenetic switches to perturbations and accounts for long-lived multidomain conformations, strikingly similar to the topologically associating domains observed in eukaryotic chromosomes.

Original languageEnglish
Article number041047
Number of pages15
JournalPhysical Review X
Volume6
Issue number4
DOIs
Publication statusPublished - 9 Dec 2016

Keywords

  • X-CHROMOSOME INACTIVATION
  • LONG-RANGE INTERACTIONS
  • HISTONE MODIFICATIONS
  • NUCLEOSOME MODIFICATION
  • HOMOPOLYMER COLLAPSE
  • TOPOLOGICAL DOMAINS
  • LIVING CELLS
  • DYNAMICS
  • MEMORY
  • KINETICS

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