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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 -
The International Journal of... 2019Mammalian oocytes/zygotes contain atypical nucleoli that are composed exclusively of a dense fibrillar material. It has been commonly accepted that these nucleoli serve... (Review)
Review
Mammalian oocytes/zygotes contain atypical nucleoli that are composed exclusively of a dense fibrillar material. It has been commonly accepted that these nucleoli serve as a repository of components that are used later on, as the embryo develops, for the construction of typical tripartite nucleoli. Indeed, when nucleoli were removed from immature oocytes (enucleolation) and these oocytes were then matured, fertilized or parthenogenetically activated, development of the produced embryos ceased after one or two cleavages with no detectable nucleoli in nuclei. This indicated that zygotic nucleoli originate exclusively from oocytes, i.e. are maternally inherited. Recently published results, however, do not support this developmental biology dogma and demonstrate that maternal nucleoli in one-cell stage embryos are necessary only during a very short time period after fertilization when they serve as a major heterochromatin organizing structures. Nevertheless, it still remains to be determined, which other functions/roles the atypical oocyte/zygote nucleoli eventually have.
Topics: Animals; Cell Nucleolus; Embryo, Mammalian; Embryonic Development; Female; Fertilization; Heterochromatin; Humans; Maternal Inheritance; Mice; Nucleoplasmins; Oocytes; Time Factors; Zygote
PubMed: 31058290
DOI: 10.1387/ijdb.180329jf -
The International Journal of... 2019The oocyte GV/GVs (germinal vesicle/germinal vesicles) and zygot PN/PNs (pronucleus/pronuclei) of some mammals contain clearly visible nucleoli which exhibit an atypical... (Review)
Review
The oocyte GV/GVs (germinal vesicle/germinal vesicles) and zygot PN/PNs (pronucleus/pronuclei) of some mammals contain clearly visible nucleoli which exhibit an atypical morphological structure. These nucleoli (NCLs) can be relatively easily manipulated, i.e. removed from GVs/PNs or eventually transferred into another oocyte/zygote. Thus, with the help of micromanipulation techniques it was possible to uncover the real function(s) they play in processes of oocyte maturation and early embryonic development. The purpose of our review is to describe briefly the micromanipulation techniques that can be used for oocyte/zygote nucleoli manipulation. Moreover, we present some examples of results that were obtained in nucleolus manipulation experiments.
Topics: Animals; Cell Nucleolus; Mice; Micromanipulation; Oocytes; Parthenogenesis; Swine; Zygote
PubMed: 31058302
DOI: 10.1387/ijdb.190002mb -
Cellular and Molecular Life Sciences :... Jun 2017Pronuclear/zygotic stage is the very first stage of life. In this period, paternal pronucleus undergoes massive chromatin remodeling called "paternal reprogramming"... (Review)
Review
Pronuclear/zygotic stage is the very first stage of life. In this period, paternal pronucleus undergoes massive chromatin remodeling called "paternal reprogramming" including protamine-histone replacement and subsequent acquisition of epigenetic modifications. Although these consecutive events are required for the initiation of maternal-zygotic transition, the precise role of paternal reprogramming and its effect on subsequent embryonic development has been largely unknown to date. Recently, various new techniques, especially next-generation sequencing (NGS) and RNAi microinjection contribute to unveil the epigenetic transition from both paternal and maternal to early preimplantation embryos, suggesting not only the simple transcriptional regulation by transcription factors but also dynamic structural alteration of chromatin to initiate the wave of zygotic gene transcription. This review summarizes such recent progress for understanding the epigenetic transition in sperm and preimplantation embryos, and further argue about its transgenerational effect.
Topics: Animals; Blastocyst; Cellular Reprogramming; Epigenesis, Genetic; Gene Expression Regulation, Developmental; Humans; Male; Spermatozoa; Zygote
PubMed: 28050628
DOI: 10.1007/s00018-016-2447-z -
Cell Proliferation Mar 2023Pre-replication complex (pre-RC) is critical for DNA replication initiation. CDT1 and MCM2 are the subunits of pre-RC, and proper regulation of CDT1 and MCM2 are...
Pre-replication complex (pre-RC) is critical for DNA replication initiation. CDT1 and MCM2 are the subunits of pre-RC, and proper regulation of CDT1 and MCM2 are necessary for DNA replication and cell proliferation. The present study aimed to explore the role of CDT1 and MCM2 in oocyte meiotic maturation and early embryonic development. The depletion and overexpression of Cdt1 and Mcm2 in oocyte and zygote were achieved by microinjecting specific siRNA and mRNA to explored their functions in oocyte meiotic maturation and embryonic development. Then, we examined the effect of CDT1 and MCM2 on other signal pathways by immunostaining the expression of related maker genes. We showed that neither depletion nor overexpression of Cdt1 affected oocyte meiotic progressions. The CDT1 was degraded in S phase and remained at a low level in G2 phase of zygote. Exogenous expression of Cdt1 in G2 phase led to embryo attest at zygote stage. Mechanistically, CDT1 overexpression induced DNA re-replication and thus DNA damage check-point activation. Protein abundance of MCM2 was stable throughout the cell cycle, and embryos with overexpressed MCM2 could develop to blastocysts normally. Overexpression or depletion of Mcm2 also had no effect on oocyte meiotic maturation. Our results indicate that pre-RC subunits CDT1 and MCM2 are not involved in oocyte meiotic maturation. In zygote, CDT1 but not MCM2 is the major regulator of DNA replication in a cell cycle dependent manner. Furthermore, its' degradation is essential for zygotes to prevent from DNA re-replication in G2 stage.
Topics: Zygote; Cell Cycle Proteins; DNA Replication; Cell Cycle; DNA
PubMed: 36479743
DOI: 10.1111/cpr.13377 -
Biochemistry. Biokhimiia Dec 2015Events, manifesting transition from maternal to zygotic period of development are studied for more than 100 years, but underlying mechanisms are not yet clear. We... (Review)
Review
Events, manifesting transition from maternal to zygotic period of development are studied for more than 100 years, but underlying mechanisms are not yet clear. We provide a brief historical overview of development of concepts and explain the specific terminology used in the field. We further discuss differences and similarities between the zygotic genome activation and in vitro reprogramming process. Finally, we envision the future research directions within the field, where biochemical methods will play increasingly important role.
Topics: Animals; Embryonic Stem Cells; Gene Expression Regulation, Developmental; Genome; Humans; Zygote
PubMed: 26878577
DOI: 10.1134/S0006297915130088 -
Trends in Genetics : TIG Nov 2016Precise elimination of maternal mRNAs plays a critical role during the maternal-to-zygotic transition (MZT) to promote developmental processing. Two new studies... (Review)
Review
Precise elimination of maternal mRNAs plays a critical role during the maternal-to-zygotic transition (MZT) to promote developmental processing. Two new studies demonstrate that, in eukaryotes, codon-mediated decay is a conserved mechanism to shape maternal mRNA stability by affecting deadenylation rate in a translation-dependent manner. These studies add to a growing body of literature suggesting that translational elongation rates are a major determinant of mRNA stability.
Topics: Codon; Eukaryota; Gene Expression Regulation, Developmental; Humans; Protein Biosynthesis; RNA Stability; RNA, Messenger; Zygote
PubMed: 27594172
DOI: 10.1016/j.tig.2016.08.007 -
Current Opinion in Cell Biology Jun 2020The fusion of two transcriptionally silent gametes, egg and sperm, generates a totipotent zygote that activates zygotic transcription to support further development.... (Review)
Review
The fusion of two transcriptionally silent gametes, egg and sperm, generates a totipotent zygote that activates zygotic transcription to support further development. Although the molecular details of zygotic genome activation (ZGA) are not well understood in most species, an emerging concept is that one or more pioneer transcription factors trigger zygotic transcription. Concomitantly, extensive changes in 3D chromatin organization occur during development. In this review, we discuss recent advances in understanding when and how genome architecture emerges in early metazoan embryos, how the zygotic genome is activated, and how these events might be coordinated. We also highlight some of the unknowns that may be critical to address in the future.
Topics: Animals; Chromatin; Embryonic Development; Gene Expression Regulation, Developmental; Genome; Transcription Factors; Zygote
PubMed: 32220807
DOI: 10.1016/j.ceb.2020.02.002 -
International Journal of Molecular... Jan 2021The maternal-to-zygotic transition (MZT), which controls maternal signaling to synthesize zygotic gene products, promotes the preimplantation development of mouse...
The maternal-to-zygotic transition (MZT), which controls maternal signaling to synthesize zygotic gene products, promotes the preimplantation development of mouse zygotes to the two-cell stage. Our previous study reported that mouse granzyme g (Gzmg), a serine-type protease, is required for the MZT. In this study, we further identified the maternal factors that regulate the promoter activity in the zygote to the two-cell stage of mouse embryos. A full-length promoter from mouse genomic DNA, FL-p (-1696~+28 nt), was cloned, and four deletion constructs of this promoter, Δ1-p (-1369~+28 nt), Δ2-p (-939~+28 nt), Δ3-p (-711~+28 nt) and Δ4-p (-417~+28 nt), were subsequently generated. Different-sized promoters were used to perform promoter assays of mouse zygotes and two-cell stage embryos. The results showed that Δ4-p promoted the highest expression level of the enhanced green fluorescent protein (EGFP) reporter in the zygotes and two-cell embryos. The data suggested that time-specific transcription factors upregulated by binding cis-elements in the -417~+28-nt promoter region. According to the results of the promoter assay, the transcription factor binding sites were predicted and analyzed with the JASPAR database, and two transcription factors, signal transducer and activator of transcription 3 (STAT3) and GA-binding protein alpha (GABPα), were identified. Furthermore, STAT3 and GABPα are expressed and located in zygote pronuclei and two-cell nuclei were confirmed by immunofluorescence staining; however, only STAT3 was recruited to the mouse zygote pronuclei and two-cell nuclei injected with the Δ4-p reporter construct. These data indicated that STAT3 is a maternal transcription factor and may upregulate to promote the MZT. Furthermore, treatment with a STAT3 inhibitor, S3I-201, caused mouse embryonic arrest at the zygote and two-cell stages. These results suggest that STAT3, a maternal protein, is a critical transcription factor and regulates transcription activity in preimplantation mouse embryos. It plays an important role in the maternal-to-zygotic transition during early embryonic development.
Topics: Animals; Blastocyst; Cell Nucleus; Embryonic Development; Female; Gene Expression Regulation, Developmental; Granzymes; Green Fluorescent Proteins; Male; Mice; Mice, Inbred ICR; Pregnancy; Promoter Regions, Genetic; STAT3 Transcription Factor; Transcription Factors; Transcriptional Activation; Zygote
PubMed: 33466434
DOI: 10.3390/ijms22010460 -
Plant Physiology May 2016Fertilization is a general feature of eukaryotic uni- and multicellular organisms to restore a diploid genome from female and male gamete haploid genomes. In most...
Fertilization is a general feature of eukaryotic uni- and multicellular organisms to restore a diploid genome from female and male gamete haploid genomes. In most animals and fucoid algae, polyspermy block occurs at the plasmogamy step. Because the polyspermy barrier in animals and in fucoid algae is incomplete, polyspermic zygotes are generated by multiple fertilization events. However, these polyspermic zygotes with extra centrioles from multiple sperms show aberrant nuclear and cell division. In angiosperms, polyspermy block functions in the egg cell and the central cell to promote faithful double fertilization, although the mechanism of polyspermy block remains unclear. In contrast to the case in animals and fucoid algae, polyspermic zygotes formed in angiosperms are not expected to die because angiosperms lack centrosomes. However, there have been no reports on the developmental profiles of polyspermic zygotes at cellular level in angiosperms. In this study, we produced polyspermic rice zygotes by electric fusion of an egg cell with two sperm cells, and monitored their developmental profiles. Two sperm nuclei and an egg nucleus fused into a zygotic nucleus, and the triploid zygote divided into a two-celled embryo via mitotic division with a typical bipolar microtubule spindle, as observed during mitosis of a diploid zygote. The two-celled proembryos further developed and regenerated into triploid plants. These findings suggest that polyspermic plant zygotes have the potential to form triploid embryos. Polyspermy in angiosperms might be a pathway for the formation of triploid plants, which can contribute significantly to the formation of autopolyploids.
Topics: Cell Division; Cell Fusion; Cell Nucleus; Cell Nucleus Division; Chromatin; Diploidy; Fertilization; Flow Cytometry; Microtubules; Mitosis; Oryza; Seeds; Triploidy; Zygote
PubMed: 26945052
DOI: 10.1104/pp.15.01953