TY - JOUR T1 - Potential energy landscapes reveal the information-theoretic nature of the epigenome JF - bioRxiv DO - 10.1101/059766 SP - 059766 AU - Garrett Jenkinson AU - Elisabet Pujadas AU - John Goutsias AU - Andrew P. Feinberg Y1 - 2016/01/01 UR - http://biorxiv.org/content/early/2016/06/18/059766.abstract N2 - 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 Shannon’s 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. ER -