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

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https://journals.aps.org/prx/abstract/10.1103/PhysRevX.6.041047
Original languageEnglish
Article number041047
Number of pages15
JournalPhysical Review X
Volume6
Issue number4
DOIs
StatePublished - 9 Dec 2016

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 threedimensional 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.

Research areas

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

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