Parent-of-Origin DNA Methylation Dynamics during Mouse Development

Yonatan Stelzer, Hao Wu, Yuelin Song, Chikdu S. Shivalila, Styliani Markoulaki, Rudolf Jaenisch*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


Parent-specific differentially methylated regions (DMRs) are established during gametogenesis and regulate parent-specific expression of imprinted genes. Monoallelic expression of imprinted genes is essential for development, suggesting that imprints are faithfully maintained in embryos and adults. To test this hypothesis, we targeted a reporter for genomic methylation to the imprinted Dlk1-Dio3 intergenic DMR (IG-DMR) to assess the methylation of both parental alleles at single-cell resolution. Biallelic gain or loss of IG-DMR methylation occurred in a small fraction of mouse embryonic stem cells, significantly affecting developmental potency. Mice carrying the reporter in either parental allele showed striking parent-specific changes in IG-DMR methylation, causing substantial and consistent tissue- and cell-type-dependent signatures in embryos and postnatal animals. Furthermore, dynamics in DNA methylation persisted during adult neurogenesis, resulting in inter-individual diversity. This substantial cell-cell DNA methylation heterogeneity implies that dynamic DNA methylation variations in the adult may be of functional importance.

Original languageEnglish (US)
Pages (from-to)3167-3180
Number of pages14
JournalCell reports
Issue number12
StatePublished - Sep 20 2016

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


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