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

Garrett Jenkinson, Elisabet Pujadas, John Goutsias, Andrew P Feinberg

Research output: Contribution to journalArticle

Abstract

Epigenetics is the study of biochemical modifications carrying information independent of DNA sequence, which are heritable through cell division. In 1940, Waddington coined the term "epigenetic landscape" as a metaphor for pluripotency and differentiation, but methylation landscapes have not yet been rigorously computed. Using principles from statistical physics and information theory, we derive epigenetic energy landscapes from whole-genome bisulfite sequencing (WGBS) data that enable us to quantify methylation stochasticity genome-wide using Shannon's entropy, associating it with chromatin structure. Moreover, we consider the Jensen-Shannon distance between sample-specific energy landscapes as a measure of epigenetic dissimilarity and demonstrate its effectiveness for discerning epigenetic differences. By 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 that leads to a powerful approach for studying its role in disease and aging.

Original languageEnglish (US)
Pages (from-to)719-729
Number of pages11
JournalNature Genetics
Volume49
Issue number5
DOIs
StatePublished - May 1 2017

ASJC Scopus subject areas

  • Genetics

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