GSE184763
Maternal Dppa2 and Dppa4 are dispensable for zygotic genome activation but important for offspring survival
Zygotic Genome Activation (ZGA) represents the initiation of transcription following fertilization. Despite its importance in shifting developmental control from primarily maternal stores in the oocyte to the embryo proper, we know little of the molecular events that initiate ZGA in vivo. Recent in vitro studies in mouse embryonic stem cells (ESCs) have revealed Developmental Pluripotency Associated 2 and 4 (Dppa2/4) as key regulators of ZGA-associated transcription. However, their roles in initiating ZGA in vivo remain unexplored. We reveal Dppa2/4 proteins are present in the nucleus at all stages of preimplantation development and associate with mitotic chromatin. We generated single and double maternal knockout mouse models to deplete maternal stores of Dppa2/4. Importantly, while fertile, Dppa2/4 maternal knockout mice had reduced litter sizes, indicating decreased offspring survival. Immunofluorescence and transcriptome analyses of 2-cell embryos revealed while ZGA took place there were subtle defects in embryos lacking maternal Dppa2/4. Strikingly, heterozygous offspring that inherited the null allele maternally had higher preweaning lethality than those that inherited the null allele paternally. Together our results show that while Dppa2/4 are dispensable for ZGA transcription, maternal stores have an important role in offspring survival, potentially via epigenetic priming of developmental genes. Overall design: Embryos were collected from 2x each mating (2x cKO x WT; 2x cKO x HET; 2x Ctrl x WT), denoted mating1 and mating2 in each file name; For the HET genotypes (included in each sample name) HET1= embryos from cKO x WT male mating (100% HET), and HET2= embryos from cKO x HET male mating (50% should be HET and 50% HOMs, according to the Mendelian ratio)