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

Nature Genetics
Garrett JenkinsonAndrew P Feinberg

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.

References

Apr 5, 2018·The New England Journal of Medicine·Andrew P Feinberg
Dec 19, 2017·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Simone EckerDirk S Paul
Nov 14, 2017·Nature Reviews. Genetics·Andrew E Teschendorff, Caroline L Relton
Oct 31, 2019·Nucleic Acids Research·Christopher T ClarksonVladimir B Teif
Dec 6, 2019·Genome Research·Polina S BelokopytovaVeniamin Fishman
Feb 28, 2020·Nucleic Acids Research·Michael SchererMarkus List
Mar 10, 2020·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Ravi TharakanLuigi Ferrucci
Apr 10, 2019·BMC Bioinformatics·Garrett JenkinsonJohn Goutsias
Jan 12, 2020·Communications Biology·Xiaobao DongMulin Jun Li
Mar 3, 2020·Epigenetics : Official Journal of the DNA Methylation Society·Michael A KoldobskiyAndrew P Feinberg
Jun 14, 2018·Frontiers in Cell and Developmental Biology·Davide MaestriniRussell C Rockne
May 3, 2020·BMC Bioinformatics·Marius WösteChristopher Schröder
Oct 18, 2020·Nature Communications·J AbanteJ Goutsias

Citations

Nov 30, 2006·Nucleic Acids Research·Axel ViselLen A Pennacchio
Nov 26, 2009·Genes & Development·Fabio SavareseRudolf Grosschedl
Jan 19, 2010·Proceedings of the National Academy of Sciences of the United States of America·Andrew P Feinberg, Rafael A Irizarry
Feb 11, 2010·Cancer Research·Hiroyasu KanedaKazuto Nishio
Mar 10, 2010·Biostatistics·Hao WuAndrew P Feinberg
Nov 11, 2010·The Journal of Biological Chemistry·Efthimia KarantzaliAndroniki Kretsovali
Jun 28, 2011·Nature Genetics·Kasper D HansenAndrew P Feinberg
Mar 13, 2012·Annual Review of Biochemistry·Howard Cedar, Yehudit Bergman
Mar 20, 2012·Cell·Elisabet Pujadas, Andrew P Feinberg
Jun 13, 2012·Proceedings of the National Academy of Sciences of the United States of America·Holger HeynManel Esteller
Jun 14, 2012·PLoS Computational Biology·Alexander FavorovSarah J Wheelan
Sep 19, 2012·Nature Reviews. Genetics·Christoph Bock
Feb 19, 2013·Cellular Signalling·Kuancan LiuXiaopeng Lan
Mar 12, 2013·Molecular Cell·Johan H Gibcus, Job Dekker
May 10, 2013·Nature Reviews. Genetics·Job DekkerLeonid A Mirny
Jun 14, 2013·Nature Reviews. Cancer·Winston Timp, Andrew P Feinberg
Aug 9, 2013·Nature·Michael J ZillerAlexander Meissner
Apr 22, 2014·Stem Cell Reports·Suchitra D GopinathThomas A Rando
Dec 2, 2014·Nature Biotechnology·Thorsten M SchlaegerGeorge Q Daley
Feb 24, 2015·Molecular Cell·Zhuojuan LuoAli Shilatifard
Aug 15, 2015·Genome Biology·Jialiang HuangGuo-Cheng Yuan

Related Concepts

Study
Hydrogen sulfite
H2S(D2S)
Protein Methylation
Genome
Cell Division
DNA Methylation
Senility
SPT6 Protein
Ion Channel

Related Feeds

Cell Aging

This feed focuses on cellular aging with emphasis on the mitochondria, autophagy, and metabolic processes associated with aging and longevity. Here is the latest research on cell aging.

Genetics & Epigenetics of Aging

This feed focuses on the genetics and epigenetics of aging. Discover the latest research here.

Aging Genetics (Keystone)

This feed focuses on aging epidemiology and genetic, epigenetic, and proteomic aspects underlying aging, as well as aging- associated biomarkers. Here the latest research in this domain.

Cell Aging (Keystone)

This feed focuses on cellular aging with emphasis on the mitochondria, autophagy, and metabolic processes associated with aging and longevity. Here is the latest research on cell aging.

Related Papers

Current Opinion in Genetics & Development
Andrew D Kelly, Jean-Pierre J Issa
Ugeskrift for laeger
M Fenger, A A Vaag
© 2020 Meta ULC. All rights reserved