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| Autores principales: | , , , |
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| Formato: | Preprint |
| Publicado: |
2025
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| Materias: | |
| Acceso en línea: | https://arxiv.org/abs/2505.13216 |
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| _version_ | 1866910015871254528 |
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| author | Olmeda, Fabrizio Gupta, Misha Bektas, Onurcan Rulands, Steffen |
| author_facet | Olmeda, Fabrizio Gupta, Misha Bektas, Onurcan Rulands, Steffen |
| contents | 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 spatio-temporal dynamics are, however, 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 non-reciprocal 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 spatio-temporal patterns which may be used by cells to control cell differentiation. |
| format | Preprint |
| id |
arxiv_https___arxiv_org_abs_2505_13216 |
| institution | arXiv |
| publishDate | 2025 |
| record_format | arxiv |
| spellingShingle | Spatio-temporal patterns of active epigenetic turnover Olmeda, Fabrizio Gupta, Misha Bektas, Onurcan Rulands, Steffen Biological Physics 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 spatio-temporal dynamics are, however, 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 non-reciprocal 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 spatio-temporal patterns which may be used by cells to control cell differentiation. |
| title | Spatio-temporal patterns of active epigenetic turnover |
| topic | Biological Physics |
| url | https://arxiv.org/abs/2505.13216 |