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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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Abstract
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.
Date issued
2016-09
URI
http://hdl.handle.net/1721.1/107925
Department
Massachusetts Institute of Technology. Department of Biology
Journal
Cell Reports
Publisher
Elsevier
Citation
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.
Version: Final published version
ISSN
2211-1247

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