Potential energy landscapes reveal the information-theoretic nature of the epigenome

Epigenetics is defined as genomic modifications carrying information independent of DNA sequence heritable through cell division. In 1940, Waddington coined the term \"epigenetic landscape\" as a metaphor for pluripotency and differentiation, but epigenetic potential energy landscapes have not yet been rigorously defined. Using well-grounded biological assumptions and principles of statistical physics and information theory, we derive potential energy landscapes from whole genome bisulfite sequencing data that allow us to quantify methylation stochasticity genome-wide and discern epigenetic differences using Shannons entropy and the Jensen-Shannon distance. We discover a \"developmental wheel\" of germ cell lineages and an association between entropy and chromatin structure. Viewing methylation maintenance as a communications system, we introduce methylation channels and show that higher-order chromatin organization can be predicted from their informational properties. Our results provide a fundamental understanding of the information-theoretic nature of the epigenome and a powerful methodology for studying its role in disease and aging.