Project description:Polycomb group (PcG) proteins are transcriptional repressors important to maintain cell identity during embryonic development. Ezh2, the catalytic subunit of the Polycomb Repressive Complex 2, is responsible for placing the epigenetic repressive mark histone H3 lysine 27 trimethylation (H3K27me3). In contrast to results in mouse models, zebrafish embryos mutant for both maternal and zygotic ezh2 (MZezh2) can form a normal body plan at 1 day post fertilization (dpf) but die at 2 dpf, exhibiting pleiotropic phenotypes. To elucidate the specificity of PcG-mediated repression during early zebrafish development, we conducted in depth analysis of the transcriptome, epigenome, and proteome of the MZezh2 mutant embryos at 1 dpf. We found that, despite modifications in the epigenetic landscape, transcriptome and proteome analysis revealed only minor changes in gene and protein expression levels.
Project description:Comprehensive quantitative proteomic study of human pre-implantation embryo stages reveal dynamic proteome landscape from M2, 8-cell and blastocyst stage, and during trophoblast stem cell (TS) differentiation. Identified key factors in early human embryos and lineage-specific trophoblast proteome profiles, correlated with transcriptomic analyses. This direct proteomic analysis provides a comprehensive analysis of the dynamic protein expression in human embryos during pre-implantation development and a powerful resource to enable further mechanistic studies on human trophoblast development and function.
Project description:Paternal exposure to a range of environmental and lifestyle factors elicits distinct changes to the sperm sncRNA profile; modifications that have significant post-fertilization consequences. Despite this knowledge, there remains limited mechanistic understanding of how paternal exposures effect the sperm sncRNA landscape. Here, we report the acute sensitivity of the sperm sncRNA profile to the potent reproductive toxicant, acrylamide. Further, we traced the differential accumulation of acrylamide responsive sncRNAs to coincide with sperm transit of the proximal (caput) segment of the epididymis, wherein acrylamide exposure altered the expression of several transcription factors implicated in the expression of acrylamide-sensitive sncRNAs. We also identified extracellular vesicles secreted from the caput epithelium in relaying altered sncRNA profiles to maturing spermatozoa, the implications of which manifest in the form of dysregulated gene expression during early embryonic development. These data provide a causative mechanistic link to account for how environmental insults can alter the sperm epigenome and compromise the transcriptomic profile of early embryos
Project description:Histones are essential for chromatin packaging and histone supply must be tightly regulated as excess histones are toxic. To drive the rapid cell cycles of the early embryo, however, excess histones are maternally deposited. Therefore, soluble histones must be buffered by histone chaperones but the chaperone necessary to stabilize soluble H3-H4 pools in the Drosophila embryo has yet to be identified. Here, we show that CG8223, the Drosophila ortholog of NASP, is a H3-H4-specific chaperone in the early embryo. NASP specifically binds to H3-H4 in the early embryo. We demonstrate that, while NASP is non-essential in Drosophila, NASP is maternal effect lethal gene. Embryos laid by NASP mutant mothers have a reduce rate of hatching and show defects in early embryogenesis. Critically, soluble H3-H4 pools are degraded in embryos laid by NASP mutant mothers. Our work identifies NASP as the critical H3-H4 histone chaperone in the Drosophila embryo.
Project description:In this study, we performed RNA-seq to elucidate how transcriptional activities of mouse oocytes and preimplantation embryos are regulated to control oocyte-to-embryo transition. Through analyzing transcriptome alterations of transgenically-modified growing oocytes, early embryos from aged female, early embryos treated with drugs disturbing proteostasis, and embryonic stem cells treated with drugs disturbing proteostasis, we identified critical roles of proteostasis in transcriptional regulation of mouse oocytes and early embryos.
