Dresden 2020 – scientific programme
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DY: Fachverband Dynamik und Statistische Physik
DY 27: Statistical Physics II
DY 27.2: Talk
Tuesday, March 17, 2020, 10:15–10:30, ZEU 118
Kinetic proofreading of epigenetic patterns — •Bahareh Kiani1, Fabrizio Olmeda2, and Steffen Rulands3 — 1Max Planck Institute for the Physics of Complex Systems, Nöthnitzer Straße 38, 01187 Dresden, Germany — 2Max Planck Institute for the Physics of Complex Systems, Nöthnitzer Straße 38, 01187 Dresden, Germany — 3Max Planck Institute for the Physics of Complex Systems, Nöthnitzer Straße 38, 01187 Dresden, Germany
During early development, the assignment of cellular identities is closely associated with the acquisition of epigenetic marks on the DNA (DNA methylation). Aberrations in the spatial arrangement of these patterns along the sequence of the DNA lead to the death of the embryo and, in adulthood, are one of the hallmarks of cancer. How, despite the limits imposed by thermodynamics, epigenetic information is precisely encoded along the DNA sequence remains to be understood. Here, we show that the paradoxical co-expression of antagonistic players in the DNA methylation machinery provides an ATP-dependent kinetic proof-reading mechanism which enhances specificity and sensitivity of these patterns by orders of magnitude. We characterise the range of possible behaviours and define optimality conditions of such a mechanism. Finally, by drawing on single-cell sequencing experiments we establish the biological significance of proofreading. Our work highlights the importance of collective, non-equilibrium processes in the establishment of epigenetic marks and sheds new lights on the epigenetic regulation of cell fate decisions in early development.