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• W2107202213 abstract "Genome-scale DNA methylation maps over early human embryogenesis and embryonic stem cell derivation provide insights into shared and unique modes of regulation when compared to the mouse model, including relationships to gene expression, transposable element activity, and maternal-specific methylation. Global patterns of DNA methylation are drastically reprogrammed in primordial germ cells and early embryonic development in mammals. This reprogramming has been well characterized in mouse embryos, but a detailed understanding of DNA methylation dynamics in human embryos is lacking. Two papers published this week [in this issue of Nature] reveal there is a massive loss of DNA methylation from most of the human genome immediately after fertilization, confirming that this epigenetic reprogramming is an evolutionarily conserved feature of development. Hongshan Guo et al. produced base-resolution maps of DNA methylation for human gametes and at several developmental stages of embryogenesis. Zachary Smith et al. obtained similar maps of DNA methylation at several developmental stages of early human embryogenesis and during derivation of human embryonic stem cell lines. The studies provide insights into differences between mouse and human methylation dynamics and the functional relationship between DNA methylation and the expression of genes and transposable elements. In mammals, cytosine methylation is predominantly restricted to CpG dinucleotides and stably distributed across the genome, with local, cell-type-specific regulation directed by DNA binding factors1,2,3. This comparatively static landscape is in marked contrast with the events of fertilization, during which the paternal genome is globally reprogrammed. Paternal genome demethylation includes the majority of CpGs, although methylation remains detectable at several notable features4,5,6,7. These dynamics have been extensively characterized in the mouse, with only limited observations available in other mammals, and direct measurements are required to understand the extent to which early embryonic landscapes are conserved8,9,10. We present genome-scale DNA methylation maps of human preimplantation development and embryonic stem cell derivation, confirming a transient state of global hypomethylation that includes most CpGs, while sites of residual maintenance are primarily restricted to gene bodies. Although most features share similar dynamics to those in mouse, maternally contributed methylation is divergently targeted to species-specific sets of CpG island promoters that extend beyond known imprint control regions. Retrotransposon regulation is also highly diverse, and transitions from maternally to embryonically expressed elements. Together, our data confirm that paternal genome demethylation is a general attribute of early mammalian development that is characterized by distinct modes of epigenetic regulation." @default.
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• W2107202213 date "2014-07-23" @default.
• W2107202213 modified "2023-10-11" @default.
• W2107202213 title "DNA methylation dynamics of the human preimplantation embryo" @default.
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• W2107202213 doi "https://doi.org/10.1038/nature13581" @default.
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