Parent-of-Origin DNA Methylation Dynamics during Mouse Development
Author(s)Stelzer, Yonatan; Wu, Hao; Song, Yuelin; Shivalila, Chikdu S.; Markoulaki, Styliani; Jaenisch, Rudolf; ... Show more Show less
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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.
DepartmentMassachusetts Institute of Technology. Department of Biology
Stelzer, Yonatan, Hao Wu, Yuelin Song, Chikdu S. Shivalila, Styliani Markoulaki, and Rudolf Jaenisch. “Parent-of-Origin DNA Methylation Dynamics During Mouse Development.” Cell Reports 16, no. 12 (September 2016): 3167–3180.
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