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Cells often exhibit different and stable phenotypes from the same DNAsequence. Robustness and plasticity of such cellular states are controlled bydiverse transcriptional and epigenetic mechanisms, among them the modificationof biochemical marks on chromatin. Here, we develop a stochastic model thatdescribes the dynamics of epigenetic marks along a given DNA region. Throughmathematical analysis, we show the emergence of bistable and persistentepigenetic states from the cooperative recruitment of modifying enzymes. Wealso find that the dynamical system exhibits a critical point and displays, inpresence of asymmetries in recruitment, a bifurcation diagram with hysteresis.These results have deep implications for our understanding of epigeneticregulation. In particular, our study allows to reconcile within the sameformalism the robust maintenance of epigenetic identity observed indifferentiated cells, the epigenetic plasticity of pluripotent cells duringdifferentiation and the effects of epigenetic misregulation in diseases.Moreover, it suggests a possible mechanism for developmental transitions wherethe system is shifted close to the critical point to benefit from highsusceptibility to developmental cues.

Bifurcation in epigenetics: implications in development, proliferation and diseases