DNA methylation entropy is associated with DNA sequence features and developmental epigenetic divergence

Abstract Epigenetic information defines tissue identity and is largely inherited in development through DNA methylation. While studied mostly for mean differences, methylation also encodes stochastic change, defined as entropy in information theory. Analyzing allele-specific methylation in 49 human...

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Published inNucleic acids research Vol. 51; no. 5; pp. 2046 - 2065
Main Authors Fang, Yuqi, Ji, Zhicheng, Zhou, Weiqiang, Abante, Jordi, Koldobskiy, Michael A, Ji, Hongkai, Feinberg, Andrew P
Format Journal Article
LanguageEnglish
Published England Oxford University Press 21.03.2023
Subjects
Animals
Computer Science
CpG Islands - genetics
DNA - genetics
DNA Methylation - genetics
Entropy
Epigenesis, Genetic
Humans
Mice
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Summary:Abstract Epigenetic information defines tissue identity and is largely inherited in development through DNA methylation. While studied mostly for mean differences, methylation also encodes stochastic change, defined as entropy in information theory. Analyzing allele-specific methylation in 49 human tissue sample datasets, we find that methylation entropy is associated with specific DNA binding motifs, regulatory DNA, and CpG density. Then applying information theory to 42 mouse embryo methylation datasets, we find that the contribution of methylation entropy to time- and tissue-specific patterns of development is comparable to the contribution of methylation mean, and methylation entropy is associated with sequence and chromatin features conserved with human. Moreover, methylation entropy is directly related to gene expression variability in development, suggesting a role for epigenetic entropy in developmental plasticity.
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The authors wish it to be known that, in their opinion, the second, third and fourth authors contribute equally.
ISSN:0305-1048
1362-4962
1362-4962
DOI:10.1093/nar/gkad050