Epigenetic memory at embryonic enhancers identified in DNA methylation maps from adult mouse tissues

Gary C. Hon, Nisha Rajagopal, Yin Shen, David F. McCleary, Feng Yue, My D. Dang, Bing Ren

Research output: Contribution to journalArticle

256 Scopus citations

Abstract

Mammalian development requires cytosine methylation, a heritable epigenetic mark of cellular memory believed to maintain a cell's unique gene expression pattern. However, it remains unclear how dynamic DNA methylation relates to cell type-specific gene expression and animal development. Here, by mapping base-resolution methylomes in 17 adult mouse tissues at shallow coverage, we identify 302,864 tissue-specific differentially methylated regions (tsDMRs) and estimate that >6.7% of the mouse genome is variably methylated. Supporting a prominent role for DNA methylation in gene regulation, most tsDMRs occur at distal cis-regulatory elements. Unexpectedly, some tsDMRs mark enhancers that are dormant in adult tissues but active in embryonic development. These 'vestigial' enhancers are hypomethylated and lack active histone modifications in adult tissues but nevertheless exhibit activity during embryonic development. Our results provide new insights into the role of DNA methylation at tissue-specific enhancers and suggest that epigenetic memory of embryonic development may be retained in adult tissues.

Original languageEnglish (US)
Pages (from-to)1198-1206
Number of pages9
JournalNature Genetics
Volume45
Issue number10
DOIs
StatePublished - Oct 2013

All Science Journal Classification (ASJC) codes

  • Genetics

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    Hon, G. C., Rajagopal, N., Shen, Y., McCleary, D. F., Yue, F., Dang, M. D., & Ren, B. (2013). Epigenetic memory at embryonic enhancers identified in DNA methylation maps from adult mouse tissues. Nature Genetics, 45(10), 1198-1206. https://doi.org/10.1038/ng.2746