Tissue-specific DNA methylation is conserved across human, mouse, and rat, and driven by primary sequence conservation

Jia Zhou, Renee L. Sears, Xiaoyun Xing, Bo Zhang, Daofeng Li, Nicole B. Rockweiler, Hyo Sik Jang, Mayank N.K. Choudhary, Hyung Joo Lee, Rebecca F. Lowdon, Jason Arand, Brianne Tabers, C. Charles Gu, Theodore J. Cicero, Ting Wang

Research output: Contribution to journalArticlepeer-review

36 Scopus citations


Background: Uncovering mechanisms of epigenome evolution is an essential step towards understanding the evolution of different cellular phenotypes. While studies have confirmed DNA methylation as a conserved epigenetic mechanism in mammalian development, little is known about the conservation of tissue-specific genome-wide DNA methylation patterns. Results: Using a comparative epigenomics approach, we identified and compared the tissue-specific DNA methylation patterns of rat against those of mouse and human across three shared tissue types. We confirmed that tissue-specific differentially methylated regions are strongly associated with tissue-specific regulatory elements. Comparisons between species revealed that at a minimum 11-37% of tissue-specific DNA methylation patterns are conserved, a phenomenon that we define as epigenetic conservation. Conserved DNA methylation is accompanied by conservation of other epigenetic marks including histone modifications. Although a significant amount of locus-specific methylation is epigenetically conserved, the majority of tissue-specific DNA methylation is not conserved across the species and tissue types that we investigated. Examination of the genetic underpinning of epigenetic conservation suggests that primary sequence conservation is a driving force behind epigenetic conservation. In contrast, evolutionary dynamics of tissue-specific DNA methylation are best explained by the maintenance or turnover of binding sites for important transcription factors. Conclusions: Our study extends the limited literature of comparative epigenomics and suggests a new paradigm for epigenetic conservation without genetic conservation through analysis of transcription factor binding sites.

Original languageEnglish
Article number724
JournalBMC genomics
Issue number1
StatePublished - Sep 12 2017


  • Comparative epigenomics
  • Comparative genomics
  • DNA methylation
  • Epigenetic conservation
  • Tissue-specific


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