Mathematical Modeling of Histone Modifications Reveals the Formation Mechanism and Function of Bivalent Chromatin

Bivalent chromatin is characterized by occupation of both activating histone modifications and repressive modifications. While bivalent known to link with many biological processes, the mechanisms responsible for its multiple functions remain unclear. Here, we develop a mathematical model that involves antagonistic H3K4me3 H3K27me3 capture key features chromatin. Three necessary conditions emergence are identified, including advantageous methylating activity over demethylating activity, frequent noise conversions modifications, sufficient nonlinearity. The first condition further confirmed analyzing experimental data from recent study. Investigation composition reveals nucleosomes carrying account no more than half at domain. We identify not only allows transitions states but also serves as stepping stone facilitate step-wise transition between state state, thus elucidate crucial roles in mediating phenotypical plasticity during cell fate determination.