  During mammalian embryo development, reprogramming of DNA methylation plays
important roles in the erasure of parental epigenetic memory and the
establishment of na\"{i}ve pluripogent cells. Multiple enzymes that regulate
the processes of methylation and demethylation work together to shape the
pattern of genome-scale DNA methylation and guid the process of cell
differentiation. Recent availability of methylome information from single-cell
whole genome bisulfite sequencing (scBS-seq) provides an opportunity to study
DNA methylation dynamics in the whole genome in individual cells, which reveal
the heterogeneous methylation distributions of enhancers in embryo stem cells
(ESCs). In this study, we developed a computational model of enhancer
methylation inheritance to study the dynamics of genome-scale DNA methylation
reprogramming during exit from pluripotency. The model enables us to track
genome-scale DNA methylation reprogramming at single-cell level during the
embryo development process, and reproduce the DNA methylation heterogeneity
reported by scBS-seq. Model simulations show that DNA methylation heterogeneity
is an intrinsic property driven by cell division along the development process,
and the collaboration between neighboring enhancers is required for
heterogeneous methylation. Our study suggest that the mechanism of genome-scale
oscillation proposed by Rulands et al. (2018) might not necessary to the DNA
methylation during exit from pluripotency.
