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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Title: A unique regulatory phase of DNA methylation in the early mammalian embryo
Author: Smith, Zachary D.; Chan, Michelle M.; Mikkelsen, Tarjei Sigurd; Gu, Hongcang; Gnirke, Andreas; Regev, Aviv; Meissner, Alexander

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Citation: Smith, Zachary D., Michelle M. Chan, Tarjei S. Mikkelsen, Hongcang Gu, Andreas Gnirke, Aviv Regev, and Alexander Meissner. 2012. A unique regulatory phase of dna methylation in the early mammalian embryo. Nature 484(7394): 339-344.
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Abstract: Summary DNA methylation is highly dynamic during mammalian embryogenesis. It is broadly accepted that the paternal genome is actively depleted of 5-methyl cytosine at fertilization, followed by passive loss that reaches a minimum at the blastocyst stage. However, this model is based on limited data, and to date no base-resolution maps exist to support and refine it. Here, we generated genome-scale DNA methylation maps in mouse gametes and through post-implantation embryogenesis. We find that the oocyte already exhibits global hypomethylation, most prominently at specific families of long interspersed element-1 and long terminal repeat retro-elements, which are disparate between gametes and resolve to lower methylation values in zygote. Surprisingly, the oocyte contributes a unique set of Differentially Methylated Regions (DMRs), including many CpG Island promoter regions, 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 resolve to hypermethylation after the blastocyst stage. Our data provide a complete 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.
Published Version: doi:10.1038/nature10960
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3331945/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Open Access Policy Articles, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#OAP
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:11729582
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