Modeling the spreading of epigenetic marks at the Oct4 promoter

Epigenetic phenomena govern a wide range of processes in biological systems from cell differentiation to cancer. Genes are activated and inactivated by the presence and absence of various epigenetic marks ranging from histone methylation and acetylation to DNA methylation. Several computational models were developed to shed light on the bistability of the expressed protein, but they are mostly conceptual inventories of mechanisms required for a switch-like behavior of promoters, without an attempt to match experimental data. Here we introduce a computational model of the promoter region of the Oct4 gene, in which we incorporate the processes of histone acetylation, histone methylation and the spreading of silencing marks via the HP1 protein complex, and DNA methylation. We show that our model’s dynamics align well with experimental results measured at the Oct4 promoter of mouse embryonic stem cells and can be adapted to describe the behavior of various promoters. We expect our approach to offer an important predictive tool to probe the strength of the epigenetic barrier to turn on a silenced gene and to predict the dependence of this barrier on the spatial organization of CpG sites.