Active DNA demethylation in mammalian preimplantation embryos: new insights and new perspectives

Abstract

DNA methylation and demethylation are crucial for modulating gene expression and regulating cell differentiation. Functions and mechanisms of DNA methylation/demethylation in mammalian embryos are still far from being understood clearly. In this review we firstly describe new insights into DNA demethylation mechanisms, and secondly introduce the differences in active DNA methylation patterns in zygotes and early embryos in various mammalian species. Thirdly, we attempt to clarify the functions of DNA demethylation in early embryos. Most importantly we summarize the importance of active DNA demethylation and its possible relevance to human IVF clinics. Finally research perspectives regarding DNA demethylation are also discussed.

Oviduct: roles in fertilization and early embryo development

“…Cell fate is not determined in the embryo before the morula stage. The early embryos repress epigenetic modification by removing DNA methylation and repressing histone modifications from the 2-cell stage until the blastocyst stage in mice 232:1 Ma et al 2012) and until the 8-cell stage in cows . However, the demethylation timing of DNA methylation in the embryo is on a gene-by-gene basis (Messerschmidt et al 2014).…”

DNA methylation and its role in the trophoblast cell lineage

“…This suggested the idea that the hypomethylation status of the genome might have some advantage for trophoblast regulation. It should be mentioned, however, that the pattern of global DNA methylation dynamics observed in mouse embryogenesis does not appear to be common among mammalian species (Ma et al, 2012). Instead, immunostaining of embryos from different mammalian species gives rather puzzling results.…”

Molecules and mechanisms controlling the active DNA demethylation of the mammalian zygotic genome

“…The Tdg could excise the 5-caC produced by TET proteins and the 5-hmUs which could be produced by deamination of 5-hmC mediated by Aicda (Ma et al, 2012). Tdg and Aicda play important roles in regulating DNA demethylation, however, both the Tdg and Aicda proteins are not detected in the mouse zygote (Hajkova et al, 2010).…”

“…During subsequent early embryo development, the zygotic genome is firstly demethylated from the zygote to morula stage and the genomic DNA is then de novo methylated at the blastocyst stage (Ma et al, 2012; Santos et al, 2002; Smith et al, 2012) (Fig. 1).…”