Epigenetic reprogramming of the zygote in mice and men: on your marks, get set, go!

Abstract

Gametogenesis (spermatogenesis and oogenesis) is accompanied by the acquisition of gender-specific epigenetic marks, such as DNA methylation, histone modifications and regulation by small RNAs, to form highly differentiated, but transcriptionally silent cell-types in preparation for fertilisation. Upon fertilisation, extensive global epigenetic reprogramming takes place to remove the previously acquired epigenetic marks and produce totipotent zygotic states. It is the aim of this review to delineate the cellular and molecular events involved in maternal, paternal and zygotic epigenetic reprogramming from the time of gametogenesis, through fertilisation, to the initiation of zygotic genome activation for preimplantation embryonic development. Recent studies have begun to uncover the indispensable functions of epigenetic players during gametogenesis, fertilisation and preimplantation embryo development, and a more comprehensive understanding of these early events will be informative for increasing pregnancy success rates, adding particular value to assisted fertility programmes.

Zygotic Genome Activation in Vertebrates

“…Conversely, de-methylation removes 5mC, largely by replication-mediated dilution or by oxidation to several intermediate methylation states (5hmC, 5fC, 5caC and others) that could each have their own effects on gene expression (Fraser and Lin, 2016). DNA methylome dynamics have been extensively studied in frog (Bogdanovic et al, 2011; Stancheva et al, 2002), fish (Jiang et al, 2013; Potok et al, 2013), mouse (Shen et al, 2014), and human (Guo et al, 2014), with notable species differences.…”

“…Taken together, these studies indicate that global methylation dynamics are not conserved across species. Moreover, the precise effects of methylation on transcription of individual genes, and intervening events between (de-)methylation and altered gene expression are unclear (Biechele et al, 2015; Fraser and Lin, 2016). …”

A single-cell transcriptomics CRISPR-activation screen identifies new epigenetic regulators of zygotic genome activation

“…In mouse, following an initial minor wave of ZGA in the late zygote, the major wave of ZGA occurs at the mid-to-late twocell embryo stage and is characterized by the transcriptional activation of thousands of genes (reviewed in Vastenhouw et al 2019;Jukam et al 2017;Svoboda 2018.;Yartseva & Giraldez 2015). Significantly, in addition to the transcriptome, the epigenetic and chromatin landscape is drastically remodelled during this transition, including reprogramming of histone post-translational modifications, global chromatin accessibility and three-dimensional structure and global DNA demethylation (reviewed in Fraser & Lin 2016;Eckersley-Maslin, Alda-Catalinas & Reik 2018;Jansz & Torres-Padilla 2019). However, while several regulators of ZGA have been identified (reviewed in Eckersley-Maslin, Alda-Catalinas & Reik 2018), a comprehensive understanding of the complex regulation of the transcriptional and epigenetic events that occur during ZGA remains elusive.…”

LIN-15B promotes enrichment of H3K9me2 on the promoters of a subset of germline genes that are repressed in somatic cells in C. elegans

“…Second, because embryos start life as the fusion of two germline cells, an egg and a sperm, they inherit an epigenetic state that has been driving germline gene expression (Furuhashi et al 2010;Rechtsteiner et al 2010;Zenk et al 2017;Tabuchi et al 2018;Kreher et al 2018). This chromatin state must be reset during development to turn off germline gene expression in differentiating somatic cells (Morgan et al 2005;Fraser and Lin 2016). There has been no investigation to date of the unique patterns of chromatin modifications or regulatory protein binding that lead to repression of germline-specific genes across somatic tissues.…”