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Current Opinion in Genetics &... Oct 2020After fertilization, mouse embryos go through preimplantation development to give rise to blastocyst. Two key molecular events, zygotic genome activation (ZGA) and the... (Review)
Review
After fertilization, mouse embryos go through preimplantation development to give rise to blastocyst. Two key molecular events, zygotic genome activation (ZGA) and the first cell lineage specification, are essential for the process. Recent advances in low-input epigenomics profiling techniques allow the analysis of these events at a molecular level, which revealed a critical role of epigenetic and chromatin reprogramming in ZGA and the first cell lineage specification. Additionally, the establishment of an in vitro embryonic stem cell (ESC) to two-cell embryo-like conversion system have also contributed to the molecular understanding of preimplantation development. In this review, we summarize recent advances in epigenetic regulation of mouse preimplantation development, point out the remaining questions, and propose strategies to tackle these questions.
Topics: Animals; Blastocyst; Embryonic Development; Embryonic Stem Cells; Epigenesis, Genetic; Female; Genome; Humans; Pregnancy; Zygote
PubMed: 32563750
DOI: 10.1016/j.gde.2020.05.015 -
Developmental Cell Apr 2022Targeted protein degradation methods offer a unique avenue to assess a protein's function in a variety of model systems. Recently, these approaches have been applied to...
Targeted protein degradation methods offer a unique avenue to assess a protein's function in a variety of model systems. Recently, these approaches have been applied to mammalian cell culture models, enabling unprecedented temporal control of protein function. However, the efficacy of these systems at the tissue and organismal levels in vivo is not well established. Here, we tested the functionality of the degradation tag (dTAG) degron system in mammalian development. We generated a homozygous knock-in mouse with a FKBP12 tag fused to negative elongation factor b (Nelfb) locus, a ubiquitously expressed regulator of transcription. In our validation of targeted endogenous protein degradation across mammalian development and adulthood, we demonstrate that irrespective of the route of administration the dTAG system is non-toxic, rapid, and efficient in embryos from the zygote-to-mid-gestation stages. Additionally, acute depletion of NELFB revealed a specific role in zygote-to-2-cell development and zygotic genome activation (ZGA).
Topics: Animals; Embryonic Development; Gene Expression Regulation, Developmental; Genome; Mammals; Mice; RNA Polymerase II; Zygote
PubMed: 35421370
DOI: 10.1016/j.devcel.2022.03.013 -
International Journal of Molecular... Jan 2024Mammalian fertilization initiates the reprogramming of oocytes and sperm, forming a totipotent zygote. During this intricate process, the zygotic genome undergoes a... (Review)
Review
Mammalian fertilization initiates the reprogramming of oocytes and sperm, forming a totipotent zygote. During this intricate process, the zygotic genome undergoes a maternal-to-zygotic transition (MZT) and subsequent zygotic genome activation (ZGA), marking the initiation of transcriptional control and gene expression post-fertilization. Histone modifications are pivotal in shaping cellular identity and gene expression in many mammals. Recent advances in chromatin analysis have enabled detailed explorations of histone modifications during ZGA. This review delves into conserved and unique regulatory strategies, providing essential insights into the dynamic changes in histone modifications and their variants during ZGA in mammals. The objective is to explore recent advancements in leading mechanisms related to histone modifications governing this embryonic development phase in depth. These considerations will be useful for informing future therapeutic approaches that target epigenetic regulation in diverse biological contexts. It will also contribute to the extensive areas of evolutionary and developmental biology and possibly lay the foundation for future research and discussion on this seminal topic.
Topics: Animals; Pregnancy; Female; Male; Zygote; Histone Code; Epigenesis, Genetic; Gene Expression Regulation, Developmental; Semen; Embryonic Development; Mammals
PubMed: 38338738
DOI: 10.3390/ijms25031459 -
Cellular Microbiology Jun 2015Schistosomiasis is a neglected tropical disease caused by infection with trematode parasites of the genus Schistosoma. Despite ongoing treatment programmes, the... (Review)
Review
Schistosomiasis is a neglected tropical disease caused by infection with trematode parasites of the genus Schistosoma. Despite ongoing treatment programmes, the prevalence of schistosomiasis has failed to decline and the disease remains a cause of severe morbidity in millions of people. Understanding the biology of egg production by schistosomes is critical since eggs allow transmission of the infection, and when trapped in host tissues induce the immune responses that are responsible for the pathologic changes that underlie disease development. Unusually among trematodes, adult schistosomes exhibit sexual dimorphism and display a fascinating codependency in that the female is dependent on the male to grow and sexually mature. Thus, virgin females are developmentally stunted compared with females from mixed-sex infections and are unable to lay eggs. Moreover, fecund female schistosomes rapidly lose the ability to produce eggs when placed in tissue culture. Here we discuss the metabolic regulation of egg production in schistosomes, and in particular the critical role played by fatty acid oxidation in this process.
Topics: Animals; Fatty Acids; Female; Fertility; Humans; Male; Oxidation-Reduction; Schistosoma; Zygote
PubMed: 25850569
DOI: 10.1111/cmi.12444 -
International Journal of Molecular... Feb 2022The double homeobox ) gene, encoding a double homeobox transcription factor, is one of the key drivers of totipotency in mice. Recent studies showed Dux was temporally... (Review)
Review
The double homeobox ) gene, encoding a double homeobox transcription factor, is one of the key drivers of totipotency in mice. Recent studies showed Dux was temporally expressed at the 2-cell stage and acted as a transcriptional activator during zygotic genome activation (ZGA) in embryos. A similar activation occurs in mouse embryonic stem cells, giving rise to 2-cell-like cells (2CLCs). Though the molecular mechanism underlying this expanded 2CLC potency caused by Dux activation has been partially revealed, the regulation mechanisms controlling Dux expression remain elusive. Here, we discuss the latest advancements in the multiple levels of regulation of Dux expression, as well as Dux function in 2CLCs transition, aiming to provide a theoretical framework for understanding the mechanisms that regulate totipotency.
Topics: Animals; Embryonic Development; Gene Expression Regulation, Developmental; Genes, Homeobox; Genome; Homeodomain Proteins; Humans; Transcription Factors; Zygote
PubMed: 35216182
DOI: 10.3390/ijms23042067 -
Cell Research Sep 2022Chromatin remodeling is essential for epigenome reprogramming after fertilization. However, the underlying mechanisms of chromatin remodeling remain to be explored....
Chromatin remodeling is essential for epigenome reprogramming after fertilization. However, the underlying mechanisms of chromatin remodeling remain to be explored. Here, we investigated the dynamic changes in nucleosome occupancy and positioning in pronucleus-stage zygotes using ultra low-input MNase-seq. We observed distinct features of inheritance and reconstruction of nucleosome positioning in both paternal and maternal genomes. Genome-wide de novo nucleosome occupancy in the paternal genome was observed as early as 1 h after the injection of sperm into ooplasm. The nucleosome positioning pattern was continually rebuilt to form nucleosome-depleted regions (NDRs) at promoters and transcription factor (TF) binding sites with differential dynamics in paternal and maternal genomes. NDRs formed more quickly on the promoters of genes involved in zygotic genome activation (ZGA), and this formation is closely linked to histone acetylation, but not transcription elongation or DNA replication. Importantly, we found that NDR establishment on the binding motifs of specific TFs might be associated with their potential pioneer functions in ZGA. Further investigations suggested that the predicted factors MLX and RFX1 played important roles in regulating minor and major ZGA, respectively. Our data not only elucidate the nucleosome positioning dynamics in both male and female pronuclei following fertilization, but also provide an efficient method for identifying key transcription regulators during development.
Topics: Animals; Chromatin Assembly and Disassembly; Female; Fertilization; Male; Mice; Nucleosomes; Regulatory Factor X1; Semen; Zygote
PubMed: 35428874
DOI: 10.1038/s41422-022-00652-8 -
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 -
FEBS Letters Sep 2018Since their discovery, the study of maternal mRNAs has led to the identification of mechanisms underlying their spatiotemporal regulation within the context of oogenesis... (Review)
Review
Since their discovery, the study of maternal mRNAs has led to the identification of mechanisms underlying their spatiotemporal regulation within the context of oogenesis and early embryogenesis. Following synthesis in the oocyte, maternal mRNAs are translationally silenced and sequestered into storage in cytoplasmic granules. At the same time, their unique distribution patterns throughout the oocyte and embryo are tightly controlled and connected to their functions in downstream embryonic processes. At certain points in oogenesis and early embryogenesis, maternal mRNAs are translationally activated to perform their functions in a timely manner. The cytoplasmic polyadenylation machinery is responsible for the translational activation of maternal mRNAs, and its role in initiating the maternal to zygotic transition events has recently come to light. Here, we summarize the current knowledge on maternal mRNA regulation, with particular focus on cytoplasmic polyadenylation as a mechanism for translational regulation.
Topics: Animals; Female; Gene Expression Regulation, Developmental; Humans; Oogenesis; Polyadenylation; RNA Interference; RNA Processing, Post-Transcriptional; RNA, Messenger; RNA, Messenger, Stored; Zygote
PubMed: 29972882
DOI: 10.1002/1873-3468.13183 -
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