RT Journal Article
SR Electronic
T1 Potential energy landscapes reveal the information-theoretic nature of the epigenome
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 059766
DO 10.1101/059766
A1 Garrett Jenkinson
A1 Elisabet Pujadas
A1 John Goutsias
A1 Andrew P. Feinberg
YR 2016
UL http://biorxiv.org/content/early/2016/06/18/059766.abstract
AB 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.