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A unique regulatory phase of DNA methylation in the early mammalian embryo
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A unique regulatory phase of DNA methylation in the early mammalian embryo
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Journal Article
A unique regulatory phase of DNA methylation in the early mammalian embryo
2012
Overview
DNA methylation is highly dynamic during mammalian embryogenesis. It is broadly accepted that the paternal genome is actively depleted of 5-methylcytosine at fertilization, followed by passive loss that reaches a minimum at the blastocyst stage. However, this model is based on limited data, and so far no base-resolution maps exist to support and refine it. Here we generate genome-scale DNA methylation maps in mouse gametes and from the zygote through post-implantation. We find that the oocyte already exhibits global hypomethylation, particularly at specific families of long interspersed element 1 and long terminal repeat retroelements, which are disparately methylated between gametes and have lower methylation values in the zygote than in sperm. Surprisingly, the oocyte contributes a unique set of differentially methylated regions (DMRs)—including many CpG island promoters—that are maintained in the early embryo but are lost upon specification and absent from somatic cells. In contrast, sperm-contributed DMRs are largely intergenic and become hypermethylated after the blastocyst stage. Our data provide a genome-scale, base-resolution timeline of DNA methylation in the pre-specified embryo, when this epigenetic modification is most dynamic, before returning to the canonical somatic pattern.
Reduced representation bisulphite sequencing is used to generate genome-scale DNA methylation maps in mouse gametes and several stages of early, pre-implantation embryogenesis, allowing a base-pair resolution timeline of the changes in DNA methylation during developmental transitions.
DNA methylation in the early embryo
This study provides a high-resolution view of dynamic DNA methylation patterns at key developmental stages in mammalian embryogenesis. Alexander Meissner and colleagues have used reduced representation bisulphite sequencing to generate genome-scale DNA methylation maps in mouse gametes and several stages of pre-implantation embryogenesis. These maps provide a base-pair-resolution timeline of the changes in DNA methylation during developmental transitions.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Animals
/ DNA
/ Embryo, Mammalian - embryology
/ Embryo, Mammalian - metabolism
/ Embryonic Development - genetics
/ Embryos
/ Female
/ Genes
/ Genetics
/ Humanities and Social Sciences
/ Long Interspersed Nucleotide Elements - genetics
/ Male
/ Mammals
/ Mice
/ Science
