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  • Open Access

Spatiotemporal Patterns of Active Epigenetic Turnover

Fabrizio Olmeda1,2,3,*, Misha Gupta1,4, Onurcan Bektas2, and Steffen Rulands1,2,†

  • *Contact author: fabrizio.olmeda@ista.ac.at
  • †Contact author: rulands@lmu.de
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PRX Life 4, 013018 – Published 9 February, 2026

DOI: https://doi.org/10.1103/89bj-79g5

Abstract

DNA methylation is a primary layer of epigenetic modification that plays a pivotal role in the regulation of development, aging, and cancer. The concurrent activity of opposing enzymes that mediate DNA methylation and demethylation gives rise to a biochemical cycle and active turnover of DNA methylation. While the ensuing biochemical oscillations have been implicated in the regulation of cell differentiation, their functional role and spatiotemporal dynamics are unknown. In this work, we demonstrate that chromatin-mediated coupling between these local biochemical cycles can lead to the emergence of phase-locked domains, regions of locally synchronized turnover activity, whose coarsening is arrested by genomic heterogeneity. We introduce a minimal model based on stochastic oscillators with constrained long-range and nonreciprocal interactions, shaped by the local chromatin organization. Through a combination of analytical theory and stochastic simulations, we predict both the degree of synchronization and the typical size of emergent phase-locked domains. We qualitatively test these predictions using single-cell sequencing data. Our results show that DNA methylation turnover exhibits surprisingly rich spatiotemporal patterns that may be used by cells to control cell differentiation.

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PRX Life 4, 013018– Published 9 February, 2026
  • Received 21 May 2025
  • Accepted 19 December 2025
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Published by the American Physical Society under the terms of the Creative Commons Attribution 4.0 International license. Further distribution of this work must maintain attribution to the author(s) and the published article's title, journal citation, and DOI.

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