Portland Press

Figure 1

$(A) At day 5 post-partum (5dpp), the majority of oocytes are non-growing (NGOs). Oocytes gradually grow postnatally in mice, which is manifested by an increase in diameter. Representative sizes of oocyte at different dpps are shown. DNA metyltransferases DNMT3A, DNMT3B and DNMT3L are increasingly expressed from early growing oocytes, which coincides with the start of DNA methylation establishment. DNMT expression peaks in FGOs, when DNA methylation is completed at approximately 40% genome coverage. Ovulation initiates maturation of the FGO and transition to MII stage, when a polar body is formed (depicted in grey) and the MII oocyte remains arrested until fertilisation. Oocyte transcription is globally repressed at the MII stage, corresponding with decrease in DNMT3 transcript levels. DNA methylation is depicted by the black line, relative expression levels for DNMTA/DNMT3B and DNMT3L are in violet and magenta, respectively. Abbreviation: dpp, days post partum. (B) Schematic representation of DNA methylation and histone marks in the FGO. Unlike the methylome of somatic cells, which shows relatively high and even levels of DNA methylation across the genome, the oocyte methylome has distinct bimodal and clustered hyper- and hypo-methylation domains. In somatic cells, promoter CpG methylation status is linked to expression, where actively transcribed genes tend to have an unmethylated promoter, but in oocytes this relationship is more ambiguous. Hypermethylated domains in the oocyte are associated with actively transcribed genes and the H3K36me3 mark. Levels of H3K36me3 positively correlate with levels of gene expression at the locus. Notably, a subset of oocyte transcripts arise from oocyte-specific or LTR-driven promoters. Hypomethylated domains span transcriptionally inactive parts of the genome and only a small fraction of the oocyte methylome falls into a partially methylated domain category; these domains tend to overlap intergenic areas. H3K4me3 in the FGO has a non-canonical distribution, where it spreads from promoters, forming broad low to medium enrichment domains over hypo- and partially methylated domains, but not hypermethylated domains. Similarly, H3K27me3 has a non-canonical distribution over hypo- and partially methylated domains, some of which overlap H3K4me3, forming bivalent chromatin. Bivalent chromatin in the oocyte does not fully recapitulate bivalency found in embryonic tissues, as the enrichment of H3K27me3 is lower. Meanwhile, H3K9me2 covers approximately a quarter of oocyte genome, again, with exclusion of hypermethylated domains. Height of the curves indicates relative enrichment of histone marks. Abbreviation: LTR, long terminal repeat.$

DNA methylation and histone mark patterns in oocyte

(A) At day 5 post-partum (5dpp), the majority of oocytes are non-growing (NGOs). Oocytes gradually grow postnatally in mice, which is manifested by an increase in diameter. Representative sizes of oocyte at different dpps are shown. DNA metyltransferases DNMT3A, DNMT3B and DNMT3L are increasingly expressed from early growing oocytes, which coincides with the start of DNA methylation establishment. DNMT expression peaks in FGOs, when DNA methylation is completed at approximately 40% genome coverage. Ovulation initiates maturation of the FGO and transition to MII stage, when a polar body is formed (depicted in grey) and the MII oocyte remains arrested until fertilisation. Oocyte transcription is globally repressed at the MII stage, corresponding with decrease in DNMT3 transcript levels. DNA methylation is depicted by the black line, relative expression levels for DNMTA/DNMT3B and DNMT3L are in violet and magenta, respectively. Abbreviation: dpp, days post partum. (B) Schematic representation of DNA methylation and histone marks in the FGO. Unlike the methylome of somatic cells, which shows relatively high and even levels of DNA methylation across the genome, the oocyte methylome has distinct bimodal and clustered hyper- and hypo-methylation domains. In somatic cells, promoter CpG methylation status is linked to expression, where actively transcribed genes tend to have an unmethylated promoter, but in oocytes this relationship is more ambiguous. Hypermethylated domains in the oocyte are associated with actively transcribed genes and the H3K36me3 mark. Levels of H3K36me3 positively correlate with levels of gene expression at the locus. Notably, a subset of oocyte transcripts arise from oocyte-specific or LTR-driven promoters. Hypomethylated domains span transcriptionally inactive parts of the genome and only a small fraction of the oocyte methylome falls into a partially methylated domain category; these domains tend to overlap intergenic areas. H3K4me3 in the FGO has a non-canonical distribution, where it spreads from promoters, forming broad low to medium enrichment domains over hypo- and partially methylated domains, but not hypermethylated domains. Similarly, H3K27me3 has a non-canonical distribution over hypo- and partially methylated domains, some of which overlap H3K4me3, forming bivalent chromatin. Bivalent chromatin in the oocyte does not fully recapitulate bivalency found in embryonic tissues, as the enrichment of H3K27me3 is lower. Meanwhile, H3K9me2 covers approximately a quarter of oocyte genome, again, with exclusion of hypermethylated domains. Height of the curves indicates relative enrichment of histone marks. Abbreviation: LTR, long terminal repeat.

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