Center for Epigenetics, Johns Hopkins University, 855 N. Wolfe St., Baltimore, MD 21205, USA.
Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
Nucleic Acids Res. 2023 Mar 21;51(5):2046-2065. doi: 10.1093/nar/gkad050.
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.
表观遗传信息定义了组织身份，并且在很大程度上通过 DNA 甲基化在发育过程中遗传。虽然主要研究平均差异，但甲基化也编码随机变化，这在信息论中定义为熵。我们分析了 49 个人类组织样本数据集的等位基因特异性甲基化，发现甲基化熵与特定的 DNA 结合基序、调节 DNA 和 CpG 密度有关。然后，我们应用信息论分析了 42 个小鼠胚胎甲基化数据集，发现甲基化熵对发育过程中时间和组织特异性模式的贡献可与甲基化均值的贡献相媲美，并且甲基化熵与与人类保守的序列和染色质特征有关。此外，甲基化熵与发育过程中基因表达的可变性直接相关，这表明表观遗传熵在发育可塑性中起作用。
