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Publication : Maternal Dppa2 and Dppa4 are dispensable for zygotic genome activation but important for offspring survival.

First Author  Kubinyecz O Year  2021
Journal  Development Volume  148
Issue  24 PubMed ID  34931676
Mgi Jnum  J:316936 Mgi Id  MGI:6842897
Doi  10.1242/dev.200191 Citation  Kubinyecz O, et al. (2021) Maternal Dppa2 and Dppa4 are dispensable for zygotic genome activation but important for offspring survival. Development 148(24):dev200191
abstractText  Zygotic genome activation (ZGA) represents the initiation of transcription following fertilisation. Despite its importance, we know little of the molecular events that initiate mammalian ZGA in vivo. Recent in vitro studies in mouse embryonic stem cells 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 that Dppa2/4 proteins are present in the nucleus at all stages of preimplantation development and associate with mitotic chromatin. We generated conditional single and double maternal knockout mouse models to deplete maternal stores of Dppa2/4. Importantly, Dppa2/4 maternal knockout mice were fertile when mated with wild-type males. Immunofluorescence and transcriptome analyses of two-cell embryos revealed that, although ZGA took place, there were subtle defects in embryos that lacked 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 although Dppa2/4 are dispensable for ZGA transcription, maternal stores have an important role in offspring survival, potentially via epigenetic priming of developmental genes.
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