Competition between local erasure and long-range spreading of a single biochemical mark leads to epigenetic bistability

Abstract

The mechanism through which cells determine their fate is intimately related to the spreading of certain biochemical (so-called epigenetic) marks along their genome. The mechanisms behind mark spreading and maintenance are not yet fully understood, and current models often assume a long-range infection-like process for the dynamics of marks, due to the polymeric nature of the chromatin fibre which allows looping between distant sites. While these existing models typically consider antagonising marks, here we propose a qualitatively different scenario which analyses the spreading of a single mark. We define a 1D stochastic model in which mark spreading/infection occurs as a long-range process whereas mark erasure/recovery is a local process, with an enhanced rate at boundaries of infected domains. In the limiting case where our model exhibits absorbing states, we find a first-order-like transition separating the marked/infected phase from the unmarked/recovered phase. This suggests that our model, in this limit, belongs to the long-range compact directed percolation universality class. The abrupt nature of the transition is retained in a more biophysically realistic situation when a basal infection/recovery rate is introduced (thereby removing absorbing states). Close to the transition there is a range of bistability where both the marked/infected and unmarked/recovered states are metastable and long lived, which provides a possible avenue for controlling fate decisions in cells. Increasing the basal infection/recovery rate, we find a second transition between a coherent (marked or unmarked) phase, and a mixed, or random, one.

arXiv comment11 pages, 7 figures, 2 appendices

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