title: Mouse oocyte methylomes at base resolution reveal genome-wide accumulation of non-CpG methylation and role of DNA methyltransferases.
abstract: DNA methylation is an epigenetic modification that plays a crucial role in normal mammalian development, retrotransposon silencing, and cellular reprogramming. Although methylation mainly occurs on the cytosine in a CG site, non-CG methylation is prevalent in pluripotent stem cells, brain, and oocytes. We previously identified non-CG methylation in several CG-rich regions in mouse germinal vesicle oocytes (GVOs), but the overall distribution of non-CG methylation and the enzymes responsible for this modification are unknown. Using amplification-free whole-genome bisulfite sequencing, which can be used with minute amounts of DNA, we constructed the base-resolution methylome maps of GVOs, non-growing oocytes (NGOs), and mutant GVOs lacking the DNA methyltransferase Dnmt1, Dnmt3a, Dnmt3b, or Dnmt3L. We found that nearly two-thirds of all methylcytosines occur in a non-CG context in GVOs. The distribution of non-CG methylation closely resembled that of CG methylation throughout the genome and showed clear enrichment in gene bodies. Compared to NGOs, GVOs were over four times more methylated at non-CG sites, indicating that non-CG methylation accumulates during oocyte growth. Lack of Dnmt3a or Dnmt3L resulted in a global reduction in both CG and non-CG methylation, showing that non-CG methylation depends on the Dnmt3a-Dnmt3L complex. Dnmt3b was dispensable. Of note, lack of Dnmt1 resulted in a slight decrease in CG methylation, suggesting that this maintenance enzyme plays a role in non-dividing oocytes. Dnmt1 may act on CG sites that remain hemimethylated in the de novo methylation process. Our results provide a basis for understanding the mechanisms and significance of non-CG methylation in mammalian oocytes.
authors: Division of Epigenomics, Medical Institute of Bioregulation, and Epigenome Network Research Center, Kyushu University, Fukuoka, Japan.
authors: Kenjiro
authors: K
authors: Shirane
authors: Hidehiro
authors: H
authors: Toh
authors: Hisato
authors: H
authors: Kobayashi
authors: Fumihito
authors: F
authors: Miura
authors: Hatsune
authors: H
authors: Chiba
authors: Takashi
authors: T
authors: Ito
authors: Tomohiro
authors: T
authors: Kono
authors: Hiroyuki
authors: H
authors: Sasaki
mesh_terms: D000818:Animals; D018899:CpG Islands; D004247:DNA / Q000378:metabolism; D019175:DNA Methylation; D016678:Genome; D051379:Mice; D009865:Oocytes / Q000378:metabolism; D009866:Oogenesis / Q000235:genetics
chemical_list: D004247:DNA
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