Limits...
De novo DNA methylation during monkey pre-implantation embryogenesis

View Article: PubMed Central - PubMed

ABSTRACT

Critical epigenetic regulation of primate embryogenesis entails DNA methylome changes. Here we report genome-wide composition, patterning, and stage-specific dynamics of DNA methylation in pre-implantation rhesus monkey embryos as well as male and female gametes studied using an optimized tagmentation-based whole-genome bisulfite sequencing method. We show that upon fertilization, both paternal and maternal genomes undergo active DNA demethylation, and genome-wide de novo DNA methylation is also initiated in the same period. By the 8-cell stage, remethylation becomes more pronounced than demethylation, resulting in an increase in global DNA methylation. Promoters of genes associated with oxidative phosphorylation are preferentially remethylated at the 8-cell stage, suggesting that this mode of energy metabolism may not be favored. Unlike in rodents, X chromosome inactivation is not observed during monkey pre-implantation development. Our study provides the first comprehensive illustration of the 'wax and wane' phases of DNA methylation dynamics. Most importantly, our DNA methyltransferase loss-of-function analysis indicates that DNA methylation influences early monkey embryogenesis.

No MeSH data available.


DNA methylation dynamics during pre-implantation embryogenesis is different between monkey and mouse. (A) Heatmap of promoter DNA methylation levels of orthologous genes during monkey and mouse pre-implantation development. Monkey genes are mapped to orthologous mouse genes from the Mouse Genome Informatics (MGI) database. (B) Gene expression and methylation levels in the promoter region of naive genes in monkey and mouse. (C) The LIF/STAT3 signaling pathway is inactivated in monkey.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC5385613&req=5

fig5: DNA methylation dynamics during pre-implantation embryogenesis is different between monkey and mouse. (A) Heatmap of promoter DNA methylation levels of orthologous genes during monkey and mouse pre-implantation development. Monkey genes are mapped to orthologous mouse genes from the Mouse Genome Informatics (MGI) database. (B) Gene expression and methylation levels in the promoter region of naive genes in monkey and mouse. (C) The LIF/STAT3 signaling pathway is inactivated in monkey.

Mentions: Comparison of DNA methylation dynamics in mouse5 and monkey embryonic development side by side by k-means clustering reveals that the methylation dynamics of monkey is significantly different from that of mouse (Figure 5A). At the blastocysts stage, most orthologous loci are hypomethylated in mouse, but remain hypermethylated in monkey. Interestingly, the pluripotency maintenance-related TGFβ and Wnt signaling pathways are differentially methylated in mouse and monkey (Figure 5A). We investigated acquisition of pluripotency between mouse and monkey within the same pre-implantation timeframe. In accordance with promoter methylation levels, many known naive-state genes, such as esrrb, zfp42, fgf4, and gbx2, are expressed at lower levels in monkey than in mouse, especially in ICM cells. Interestingly, members of the LIF/STAT3 signaling pathway, which plays an important role in maintaining naive state of mouse embryonic stem cells, are differentially regulated in monkey and mouse both at the DNA methylation and RNA expression levels. We found methylation levels in the promoters of lif, socs3, and jak2 are high, and their expression is more suppressed, in monkey (Figure 5B and 5C). Our data provide evidence that naive state acquisition is regulated differently in primate and mouse.


De novo DNA methylation during monkey pre-implantation embryogenesis
DNA methylation dynamics during pre-implantation embryogenesis is different between monkey and mouse. (A) Heatmap of promoter DNA methylation levels of orthologous genes during monkey and mouse pre-implantation development. Monkey genes are mapped to orthologous mouse genes from the Mouse Genome Informatics (MGI) database. (B) Gene expression and methylation levels in the promoter region of naive genes in monkey and mouse. (C) The LIF/STAT3 signaling pathway is inactivated in monkey.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5385613&req=5

fig5: DNA methylation dynamics during pre-implantation embryogenesis is different between monkey and mouse. (A) Heatmap of promoter DNA methylation levels of orthologous genes during monkey and mouse pre-implantation development. Monkey genes are mapped to orthologous mouse genes from the Mouse Genome Informatics (MGI) database. (B) Gene expression and methylation levels in the promoter region of naive genes in monkey and mouse. (C) The LIF/STAT3 signaling pathway is inactivated in monkey.
Mentions: Comparison of DNA methylation dynamics in mouse5 and monkey embryonic development side by side by k-means clustering reveals that the methylation dynamics of monkey is significantly different from that of mouse (Figure 5A). At the blastocysts stage, most orthologous loci are hypomethylated in mouse, but remain hypermethylated in monkey. Interestingly, the pluripotency maintenance-related TGFβ and Wnt signaling pathways are differentially methylated in mouse and monkey (Figure 5A). We investigated acquisition of pluripotency between mouse and monkey within the same pre-implantation timeframe. In accordance with promoter methylation levels, many known naive-state genes, such as esrrb, zfp42, fgf4, and gbx2, are expressed at lower levels in monkey than in mouse, especially in ICM cells. Interestingly, members of the LIF/STAT3 signaling pathway, which plays an important role in maintaining naive state of mouse embryonic stem cells, are differentially regulated in monkey and mouse both at the DNA methylation and RNA expression levels. We found methylation levels in the promoters of lif, socs3, and jak2 are high, and their expression is more suppressed, in monkey (Figure 5B and 5C). Our data provide evidence that naive state acquisition is regulated differently in primate and mouse.

View Article: PubMed Central - PubMed

ABSTRACT

Critical epigenetic regulation of primate embryogenesis entails DNA methylome changes. Here we report genome-wide composition, patterning, and stage-specific dynamics of DNA methylation in pre-implantation rhesus monkey embryos as well as male and female gametes studied using an optimized tagmentation-based whole-genome bisulfite sequencing method. We show that upon fertilization, both paternal and maternal genomes undergo active DNA demethylation, and genome-wide de novo DNA methylation is also initiated in the same period. By the 8-cell stage, remethylation becomes more pronounced than demethylation, resulting in an increase in global DNA methylation. Promoters of genes associated with oxidative phosphorylation are preferentially remethylated at the 8-cell stage, suggesting that this mode of energy metabolism may not be favored. Unlike in rodents, X chromosome inactivation is not observed during monkey pre-implantation development. Our study provides the first comprehensive illustration of the 'wax and wane' phases of DNA methylation dynamics. Most importantly, our DNA methyltransferase loss-of-function analysis indicates that DNA methylation influences early monkey embryogenesis.

No MeSH data available.