The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
A unique regulatory phase of DNA methylation in the early mammalian embryo
Open accessAbstract
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.
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Cites
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Genome-scale DNA methylation maps of pluripotent and differentiated cells
Meissner, A., Mikkelsen, T. S., Gu, H., Wernig, M., Hanna, J., Sivachenko, A., Zhang, X., Bernstein, B. E., Nusbaum, C., Jaffe, D. B., et al. (2008) · Nature · doi:10.1038/nature07107 · Cited by 2,536
Self-citationTET1 and hydroxymethylcytosine in transcription and DNA methylation fidelity
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Uncovering the role of 5-hydroxymethylcytosine in the epigenome
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Cited by
DNA methylation: roles in mammalian development
Smith, Z. D., & Meissner, A. (2013) · Nature Reviews Genetics · doi:10.1038/nrg3354 · Cited by 3,045
Self-citationTransgenerational epigenetic inheritance: myths and mechanisms
Heard, E., & Martienssen, R. A. (2014) · Cell · doi:10.1016/j.cell.2014.02.045 · Cited by 1,864
TET-mediated active DNA demethylation: mechanism, function and beyond
Wu, X., & Zhang, Y. (2017) · Nature Reviews Genetics · doi:10.1038/nrg.2017.33 · Cited by 1,661
TET enzymes, TDG and the dynamics of DNA demethylation
Kohli, R. M., & Zhang, Y. (2013) · Nature · doi:10.1038/nature12750 · Cited by 1,623
Charting a dynamic DNA methylation landscape of the human genome
Ziller, M. J., Gu, H., Müller, F., Donaghey, J., Tsai, L. T.-Y., Kohlbacher, O., De Jager, P. L., Rosen, E. D., Bennett, D. A., Bernstein, B. E., et al. (2013) · Nature · doi:10.1038/nature12433 · Cited by 1,357
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Metadata
- Authors
- Smith, Z. D., Chan, M. M., Mikkelsen, T. S., Gu, H., Gnirke, A., Regev, A., & Meissner, A.
- Venue
- Nature
- Published
- 2012-03-28
- Volume
- 484
- Issue
- 7394
- Pages
- 339-344
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2096391240
- Cited by
- 971
- References
- 9
- FWCI
- 40.20
- Type
- journal article
- Language
- en
- Open access
- green
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