A unique regulatory phase of DNA methylation in the early mammalian embryo
By Zachary D. Smith, Michelle M. Chan, Tarjei S. Mikkelsen, H. Gu, Andreas Gnirke, Aviv Regev, Alexander Meissner. Nature, 2012
985 citations recorded by the source corpus.
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.
Subfields: Genetics, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/54a7e03ed2e57329f93e55d526615ac87d8b5772
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Citations in the corpus
- Single-Cell DNA Methylome Sequencing and Bioinformatic Inference of Epigenomic Cell-State Dynamics (2015, methodology): “RRBS has also been applied to populations of about 100 cells from mouse embryos and oocytes (Smallwood et al., 2011; Smith et al., 2012), yielding data for 1–2 million CpGs out of the approximately 21.”
- A Bayesian hierarchical model to detect differentially methylated loci from single nucleotide resolution sequencing data (2014, methodology): “4%) were hypermethylated in oocytes (Figure 6), which is consistent with the original findings (21).”
- methylKit: a comprehensive R package for the analysis of genome-wide DNA methylation profiles (2012, background): “[9] investigated methylation profiles with RRBS experiments on gametes and zygote and summarized methylation information on 100bp tiles across the genome.”
- The Dynamics of Genome-wide DNA Methylation Reprogramming in Mouse Primordial Germ Cells (2012, methodology): “…the inner cell mass are globally hypomethylated, as a result of epigenetic reprogramming during preimplantation development, but upon implantation rapid de novo methylation occurs primarily in the epiblast (Howlett and Reik, 1991; Santos et al., 2002; Borgel et al., 2010; Smith et al., 2012).”
- Reversing DNA Methylation: Mechanisms, Genomics, and Biological Functions (2014, positive): “…DNA demethylation, a subset of maternally derived methylated CpG-rich sequences, including many maternal ICRs and some retroviral repeats such as the intracisternal A particle (IAP) type, remain fully or partially methylated (Lane et al., Cell 15 2003; Smallwood et al., 2011; Smith et al., 2012).”
- Transgenerational Epigenetic Inheritance: myths and mechanisms (2014, neutral): “In the mouse germline and also early postfertilization, the two parental genomes undergo extensive DNA demethylation via both active and passive mechanisms, leading to equivalent hypomethylated states in early cleavage stages accompanied by dynamic changes in histone modification (Hackett and Surani”