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PLoS Biology Jan 2021To ensure genome stability, sexually reproducing organisms require that mating brings together exactly 2 haploid gametes and that meiosis occurs only in diploid zygotes....
To ensure genome stability, sexually reproducing organisms require that mating brings together exactly 2 haploid gametes and that meiosis occurs only in diploid zygotes. In the fission yeast Schizosaccharomyces pombe, fertilization triggers the Mei3-Pat1-Mei2 signaling cascade, which represses subsequent mating and initiates meiosis. Here, we establish a degron system to specifically degrade proteins postfusion and demonstrate that mating blocks not only safeguard zygote ploidy but also prevent lysis caused by aberrant fusion attempts. Using long-term imaging and flow-cytometry approaches, we identify previously unrecognized and independent roles for Mei3 and Mei2 in zygotes. We show that Mei3 promotes premeiotic S-phase independently of Mei2 and that cell cycle progression is both necessary and sufficient to reduce zygotic mating behaviors. Mei2 not only imposes the meiotic program and promotes the meiotic cycle, but also blocks mating behaviors independently of Mei3 and cell cycle progression. Thus, we find that fungi preserve zygote ploidy and survival by at least 2 mechanisms where the zygotic fate imposed by Mei2 and the cell cycle reentry triggered by Mei3 synergize to prevent zygotic mating.
Topics: Cell Cycle; Cell Cycle Proteins; Fungal Proteins; Genes, Fungal; Mating Factor; Meiosis; Organisms, Genetically Modified; Ploidies; RNA-Binding Proteins; Recombination, Genetic; Schizosaccharomyces; Schizosaccharomyces pombe Proteins; Zygote
PubMed: 33406066
DOI: 10.1371/journal.pbio.3001067 -
Cell Reports Jun 2020After fertilization, sperm and oocyte nuclei are rapidly remodeled to form swollen pronuclei (PN) in mammalian zygotes, and the proper formation and function of PN are...
After fertilization, sperm and oocyte nuclei are rapidly remodeled to form swollen pronuclei (PN) in mammalian zygotes, and the proper formation and function of PN are key to producing totipotent zygotes. However, how mature PN are formed has been unclear. We find that filamentous actin (F-actin) assembles in the PN of mouse zygotes and is required for fully functional PN. The perturbation of nuclear actin dynamics in zygotes results in the misregulation of genes related to genome integrity and abnormal development of mouse embryos. We show that nuclear F-actin ensures DNA damage repair, thus preventing the activation of a zygotic checkpoint. Furthermore, optogenetic control of cofilin nuclear localization reveals the dynamically regulated F-actin nucleoskeleton in zygotes, and its timely disassembly is needed for developmental progression. Nuclear F-actin is a hallmark of totipotent zygotic PN, and the temporal regulation of its polymerized state is necessary for normal embryonic development.
Topics: Actin Cytoskeleton; Actin Depolymerizing Factors; Actins; Animals; Cell Cycle Checkpoints; Cell Nucleus; Cell Survival; Checkpoint Kinase 1; DNA Damage; Embryo, Mammalian; Embryonic Development; Gene Expression Regulation, Developmental; Imaging, Three-Dimensional; Light; Mice, Inbred ICR; Mitosis; Polymerization; Up-Regulation; Zygote
PubMed: 32610125
DOI: 10.1016/j.celrep.2020.107824 -
Molecular Plant Sep 2021Fertilization constitutes a critical step in the plant life cycle during which the gamete genomes undergo chromatin dynamics in preparation for embryogenesis. In...
Fertilization constitutes a critical step in the plant life cycle during which the gamete genomes undergo chromatin dynamics in preparation for embryogenesis. In mammals, parental chromatin is extensively reprogrammed through the global erasure of DNA methylation. However, in flowering plants it remains unclear whether and how DNA methylation is remodeled in gametes and after fertilization in the zygote. In this study, we characterize DNA methylation patterns and investigate the function of DNA glycosylases in rice eggs, sperm, and unicellular zygotes and during embryogenesis. We found that DNA methylation is locally reconfigured after fertilization and is intensified during embryogenesis. Genetic, epigenomic, and transcriptomic analysis revealed that three rice DNA glycosylases, DNG702, DNG701, and DNG704, demethylate DNA at distinct genomic regions in the gametes and the zygote, and are required for zygotic gene expression and development. Collectively, these results indicate that active DNA demethylation takes place in the gametes and the zygote to locally remodel DNA methylation, which is critical for egg and zygote gene expression and reproduction in rice.
Topics: Arabidopsis; Chromatin; DNA Methylation; DNA, Plant; Germ Cells, Plant; Oryza; Plant Development; Zygote
PubMed: 34116223
DOI: 10.1016/j.molp.2021.06.006 -
Stem Cells and Development Jul 2019The mammalian zygote is described as a totipotent cell in the literature, but this characterization is elusive ignoring the molecular underpinnings. Totipotency can... (Review)
Review
The mammalian zygote is described as a totipotent cell in the literature, but this characterization is elusive ignoring the molecular underpinnings. Totipotency can connote genetic totipotency, epigenetic totipotency, or the reprogramming capacity of a cell to epigenetic totipotency. Here, the implications of these concepts are discussed in the context of the properties of the zygote. Although genetically totipotent as any diploid somatic cell is, a zygote seems not totipotent transcriptionally, epigenetically, or functionally. Yet, a zygote may retain most of the key factors from its parental oocyte to reprogram an implanted differentiated genome or the zygote genome toward totipotency. This totipotent reprogramming process may extend to blastomeres in the two-cell-stage embryo. Thus, a revised alternative model of mammalian cellular totipotency is proposed, in which an epigenetically totipotent cell exists after the major embryonic genome activation and before the separation of the first two embryonic lineages.
Topics: Animals; Cell Differentiation; Embryo, Mammalian; Epigenesis, Genetic; Gene Expression Regulation, Developmental; Humans; Zygote
PubMed: 31122174
DOI: 10.1089/scd.2019.0057 -
Development (Cambridge, England) Jul 2021Understanding the mechanisms of embryonic cell cycles is a central goal of developmental biology, as the regulation of the cell cycle must be closely coordinated with...
Understanding the mechanisms of embryonic cell cycles is a central goal of developmental biology, as the regulation of the cell cycle must be closely coordinated with other events during early embryogenesis. Quantitative imaging approaches have recently begun to reveal how the cell cycle oscillator is controlled in space and time, and how it is integrated with mechanical signals to drive morphogenesis. Here, we discuss how the Drosophila embryo has served as an excellent model for addressing the molecular and physical mechanisms of embryonic cell cycles, with comparisons to other model systems to highlight conserved and species-specific mechanisms. We describe how the rapid cleavage divisions characteristic of most metazoan embryos require chemical waves and cytoplasmic flows to coordinate morphogenesis across the large expanse of the embryo. We also outline how, in the late cleavage divisions, the cell cycle is inter-regulated with the activation of gene expression to ensure a reliable maternal-to-zygotic transition. Finally, we discuss how precise transcriptional regulation of the timing of mitosis ensures that tissue morphogenesis and cell proliferation are tightly controlled during gastrulation.
Topics: Animals; CDC2 Protein Kinase; Cell Cycle; Cell Cycle Checkpoints; Drosophila; Drosophila Proteins; Embryo, Mammalian; Embryo, Nonmammalian; Embryonic Development; Gene Expression Regulation, Developmental; Mitosis; Morphogenesis; Xenopus; Zygote
PubMed: 34164654
DOI: 10.1242/dev.193128 -
Journal of Experimental Zoology. Part... Dec 2021Flowering plants (angiosperms) perform a unique double fertilization in which two sperm cells fuse with two female gamete cells in the embryo sac to develop a seed.... (Review)
Review
Flowering plants (angiosperms) perform a unique double fertilization in which two sperm cells fuse with two female gamete cells in the embryo sac to develop a seed. Furthermore, during land plant evolution, the mode of sexual reproduction has been modified dramatically from motile sperm in the early-diverging land plants, such as mosses and ferns as well as some gymnosperms (Ginkgo and cycads) to nonmotile sperm that are delivered to female gametes by the pollen tube in flowering plants. Recent studies have revealed the cellular dynamics and molecular mechanisms for the complex series of double fertilization processes and elucidated differences and similarities between animals and plants. Here, together with a brief comparison with animals, we review the current understanding of flowering plant zygote dynamics, covering from gamete nuclear migration, karyogamy, and polyspermy block, to zygotic genome activation as well as asymmetrical division of the zygote. Further analyses of the detailed molecular and cellular mechanisms of flowering plant fertilization should shed light on the evolution of the unique sexual reproduction of flowering plants.
Topics: Animals; Fertilization; Germ Cells; Magnoliopsida; Seeds; Zygote
PubMed: 32638525
DOI: 10.1002/jez.b.22981 -
Cell Reports Sep 2023The transcription factor DUX4 regulates a portion of the zygotic gene activation (ZGA) program in the early embryo. Many cancers express DUX4 but it is unknown whether...
The transcription factor DUX4 regulates a portion of the zygotic gene activation (ZGA) program in the early embryo. Many cancers express DUX4 but it is unknown whether this generates cells similar to early embryonic stem cells. Here we identified cancer cell lines that express DUX4 and showed that DUX4 is transiently expressed in a small subset of the cells. DUX4 expression activates the DUX4-regulated ZGA transcriptional program, the subsequent 8C-like program, and markers of early embryonic lineages, while suppressing steady-state and interferon-induced MHC class I expression. Although DUX4 was expressed in a small number of cells under standard culture conditions, DNA damage or changes in growth conditions increased the fraction of cells expressing DUX4 and its downstream programs. Our demonstration that transient expression of endogenous DUX4 in cancer cells induces a metastable early embryonic stem cell program and suppresses antigen presentation has implications for cancer growth, progression, and immune evasion.
Topics: Humans; Cell Line; Genes, Homeobox; Homeodomain Proteins; Muscular Dystrophy, Facioscapulohumeral; Neoplasms; Transcription Factors; Zygote
PubMed: 37691147
DOI: 10.1016/j.celrep.2023.113114 -
Journal of Assisted Reproduction and... Nov 2023The prevailing assumption has been that the human spermatozoon provides only one centriole to the zygote: the proximal centriole, with a canonical, cylinder-like shape.... (Review)
Review
The prevailing assumption has been that the human spermatozoon provides only one centriole to the zygote: the proximal centriole, with a canonical, cylinder-like shape. This overly simplistic view has come under challenge since discovering that the human spermatozoon provides a second, atypical centriole to the zygote. The study of human zygotes is challenging for ethical reasons, and bovine zygotes provide an important model due to a similarity in centrosome embryonic inherence and function. Detailed ultrastructural analyses by Uzbekov and colleagues identify the persistence of atypical centrioles in bovine early embryos, raising questions about the original single-centriole model. Whether the parental origin of nascent atypical centrioles or their wide structural diversity and deviation from the canonical centriolar form in blastomeres constitutes sufficient evidence to warrant a reconsideration of the single-centriole model is discussed herein. Because previous human studies identified only one canonical centriole in the zygote, atypical centrioles are likely present in the early human embryo; therefore, it is time to rethink the role of paternal centrioles in human development.
Topics: Male; Humans; Animals; Cattle; Centrioles; Spermatozoa; Centrosome; Zygote; Embryonic Development; Mammals
PubMed: 37713143
DOI: 10.1007/s10815-023-02927-4 -
Genome Research Feb 2022The zygote, a totipotent stem cell, is crucial to the life cycle of sexually reproducing organisms. It is produced by the fusion of two differentiated cells-the egg and...
The zygote, a totipotent stem cell, is crucial to the life cycle of sexually reproducing organisms. It is produced by the fusion of two differentiated cells-the egg and sperm, which in plants have radically different siRNA transcriptomes from each other and from multicellular embryos. Owing to technical challenges, the epigenetic changes that accompany the transition from differentiated gametes to totipotent zygote are poorly understood. Because siRNAs serve as both regulators and outputs of the epigenome, we characterized small RNA transcriptomes of zygotes from rice. Zygote small RNAs exhibit extensive maternal carryover and an apparent lack of paternal contribution, indicated by absence of sperm signature siRNAs. Zygote formation is accompanied by widespread redistribution of 24-nt siRNAs relative to gametes, such that ∼70% of the zygote siRNA loci do not overlap any egg cell siRNA loci. Newly detected siRNA loci in zygote are gene-proximal and not associated with centromeric heterochromatin, similar to canonical siRNAs, in sharp contrast to gametic siRNA loci that are gene-distal and heterochromatic. In addition, zygote but not egg siRNA loci are associated with high DNA methylation in the mature embryo. Thus, the zygote begins transitioning before the first embryonic division to an siRNA profile that is associated with future RdDM in embryogenesis. These findings indicate that, in addition to changes in gene expression, the transition to totipotency in the plant zygote is accompanied by resetting of the epigenetic reprogramming that occurred during gamete formation.
Topics: DNA Methylation; Epigenesis, Genetic; Oryza; RNA, Small Interfering; Zygote
PubMed: 34949668
DOI: 10.1101/gr.275981.121 -
Nature Cell Biology Apr 2020The importance of germline-inherited post-translational histone modifications on priming early mammalian development is just emerging. Histone H3 lysine 9 (H3K9)...
The importance of germline-inherited post-translational histone modifications on priming early mammalian development is just emerging. Histone H3 lysine 9 (H3K9) trimethylation is associated with heterochromatin and gene repression during cell-fate change, whereas histone H3 lysine 4 (H3K4) trimethylation marks active gene promoters. Mature oocytes are transcriptionally quiescent and possess remarkably broad domains of H3K4me3 (bdH3K4me3). It is unknown which factors contribute to the maintenance of the bdH3K4me3 landscape. Lysine-specific demethylase 4A (KDM4A) demethylates H3K9me3 at promoters marked by H3K4me3 in actively transcribing somatic cells. Here, we report that KDM4A-mediated H3K9me3 demethylation at bdH3K4me3 in oocytes is crucial for normal pre-implantation development and zygotic genome activation after fertilization. The loss of KDM4A in oocytes causes aberrant H3K9me3 spreading over bdH3K4me3, resulting in insufficient transcriptional activation of genes, endogenous retroviral elements and chimeric transcripts initiated from long terminal repeats during zygotic genome activation. The catalytic activity of KDM4A is essential for normal epigenetic reprogramming and pre-implantation development. Hence, KDM4A plays a crucial role in preserving the maternal epigenome integrity required for proper zygotic genome activation and transfer of developmental control to the embryo.
Topics: Animals; Embryo Implantation; Embryo, Mammalian; Female; Fertilization; Heterochromatin; Histone Demethylases; Histones; Male; Metaphase; Methylation; Mice; Mice, Knockout; Oocytes; Promoter Regions, Genetic; Protein Processing, Post-Translational; Transcription, Genetic; Zygote
PubMed: 32231309
DOI: 10.1038/s41556-020-0494-z