DNA methylation entropy is associated with DNA sequence features and developmental epigenetic divergence

Epigenetic information defines tissue identity and is largely inherited in development through DNA methylation. While studied mostly for mean differences, methylation also encodes stochastic change, defined as entropy in information theory. Analyzing allele-specific methylation in 49 human tissue sample datasets, we find that methylation entropy is associated with specific DNA binding motifs, regulatory DNA, and CpG density. Then applying information theory to 42 mouse embryo methylation datasets, we find that the contribution of methylation entropy to time- and tissue-specific patterns of development is comparable to the contribution of methylation mean, and methylation entropy is associated with sequence and chromatin features conserved with human. Moreover, methylation entropy is directly related to gene expression variability in development, suggesting a role for epigenetic entropy in developmental plasticity.

Automated summary

Epigenetic information, inherited through DNA methylation, plays a crucial role in defining tissue identity. This study reveals that methylation entropy, which represents stochastic changes in DNA methylation, is associated with specific DNA binding motifs, regulatory DNA, and CpG density. Additionally, the contribution of methylation entropy to developmental patterns is comparable to that of methylation mean, and it is associated with conserved sequence and chromatin features. Furthermore, methylation entropy is directly related to gene expression variability in development, suggesting its involvement in developmental plasticity.