Maternal Dppa2 and Dppa4 are dispensable for zygotic genome activation but important for offspring survival
| العنوان: | Maternal Dppa2 and Dppa4 are dispensable for zygotic genome activation but important for offspring survival |
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| المؤلفون: | Oana Kubinyecz, Fatima Santos, Deborah Drage, Wolf Reik, Melanie A. Eckersley-Maslin |
| المصدر: | Development (Cambridge, England) article-version (VoR) Version of Record |
| بيانات النشر: | The Company of Biologists, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Mice, Knockout, Transcriptional Activation, Genome, Mouse, Zygote, Embryonic Development, Gene Expression Regulation, Developmental, Nuclear Proteins, Mouse Embryonic Stem Cells, Dppa2, Chromatin, Dppa4, Zygotic genome activation, Mice, Embryo, Maternal factors, Animals, Epigenetics, Molecular Biology, Transcription Factors, Research Article, Developmental Biology |
| الوصف: | 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. Summary: Conditional knockout mouse models reveal maternal stores of Dppa2 and Dppa4 are dispensable for zygotic genome activation, contrasting findings in embryonic stem cells. However, both maternal and zygotic Dppa2/4 are required for development. |
| تدمد: | 1477-9129 0950-1991 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::42f40f3d0ad6c14cce0bdfa70d19d463 https://doi.org/10.1242/dev.200191 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....42f40f3d0ad6c14cce0bdfa70d19d463 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14779129 09501991 |
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