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Developmental Cell Aug 2017The first major developmental transition in vertebrate embryos is the maternal-to-zygotic transition (MZT) when maternal mRNAs are degraded and zygotic transcription... (Review)
Review
The first major developmental transition in vertebrate embryos is the maternal-to-zygotic transition (MZT) when maternal mRNAs are degraded and zygotic transcription begins. During the MZT, the embryo takes charge of gene expression to control cell differentiation and further development. This spectacular organismal transition requires nuclear reprogramming and the initiation of RNAPII at thousands of promoters. Zygotic genome activation (ZGA) is mechanistically coordinated with other embryonic events, including changes in the cell cycle, chromatin state, and nuclear-to-cytoplasmic component ratios. Here, we review progress in understanding vertebrate ZGA dynamics in frogs, fish, mice, and humans to explore differences and emphasize common features.
Topics: Animals; Cellular Reprogramming; Embryo, Mammalian; Embryo, Nonmammalian; Gene Expression Regulation, Developmental; Genome; Vertebrates; Zygote
PubMed: 28829942
DOI: 10.1016/j.devcel.2017.07.026 -
Molecular Aspects of Medicine Oct 2013Prior to activation of the embryonic genome, the initiating events of mammalian development are under maternal control and include fertilization, the block to polyspermy... (Review)
Review
Prior to activation of the embryonic genome, the initiating events of mammalian development are under maternal control and include fertilization, the block to polyspermy and processing sperm DNA. Following gamete union, the transcriptionally inert sperm DNA is repackaged into the male pronucleus which fuses with the female pronucleus to form a 1-cell zygote. Embryonic transcription begins during the maternal to zygotic transfer of control in directing development. This transition occurs at species-specific times after one or several rounds of blastomere cleavage and is essential for normal development. However, even after activation of the embryonic genome, successful development relies on stored maternal components without which embryos fail to progress beyond initial cell divisions. Better understanding of the molecular basis of maternal to zygotic transition including fertilization, the activation of the embryonic genome and cleavage-stage development will provide insight into early human development that should translate into clinical applications for regenerative medicine and assisted reproductive technologies.
Topics: Animals; DNA Methylation; Embryonic Development; Female; Fertilization; Genome; Humans; Male; Mammals; Mice; Reproductive Techniques, Assisted; Spermatozoa; Transcription, Genetic; Zygote
PubMed: 23352575
DOI: 10.1016/j.mam.2013.01.003 -
Cell Stem Cell Mar 2022The activation of the embryonic genome marks the first major wave of transcription in the developing organism. Zygotic genome activation (ZGA) in mouse 2-cell embryos...
The activation of the embryonic genome marks the first major wave of transcription in the developing organism. Zygotic genome activation (ZGA) in mouse 2-cell embryos and 8-cell embryos in humans is crucial for development. Here, we report the discovery of human 8-cell-like cells (8CLCs) among naive embryonic stem cells, which transcriptionally resemble the 8-cell human embryo. They express ZGA markers, including ZSCAN4 and LEUTX, and transposable elements, such as HERVL and MLT2A1. 8CLCs show reduced SOX2 levels and can be identified using TPRX1 and H3.Y marker proteins in vitro. Overexpression of the transcription factor DUX4 and spliceosome inhibition increase human ZGA-like transcription. Excitingly, the 8CLC markers TPRX1 and H3.Y are also expressed in ZGA-stage 8-cell human embryos and may thus be relevant in vivo. 8CLCs provide a unique opportunity to characterize human ZGA-like transcription and might provide critical insights into early events in embryogenesis in humans.
Topics: Animals; Embryonic Development; Gene Expression Regulation, Developmental; Genome, Human; Humans; Mice; Transcription Factors; Zygote
PubMed: 35216671
DOI: 10.1016/j.stem.2022.01.014 -
Science Advances Feb 2022Translational regulation plays an important role in gene expression and function. Although the transcriptional dynamics of mouse preimplantation embryos have been well...
Translational regulation plays an important role in gene expression and function. Although the transcriptional dynamics of mouse preimplantation embryos have been well characterized, the global mRNA translation landscape and the master regulators of zygotic genome activation (ZGA) remain unknown. Here, by developing and applying a low-input ribosome profiling (LiRibo-seq) technique, we profiled the mRNA translation landscape in mouse preimplantation embryos and revealed the translational dynamics during mouse preimplantation development. We identified a marked translational transition from MII oocytes to zygotes and demonstrated that active translation of maternal mRNAs is essential for maternal-to-zygotic transition (MZT). We further showed that two maternal factors, Smarcd2 and Cyclin T2, whose translation is activated in zygotes, are required for chromatin reprogramming and ZGA, respectively. Our study thus not only filled in a knowledge gap on translational regulation during mammalian preimplantation development but also revealed insights into the critical function of maternal mRNA translation in MZT.
Topics: Animals; Embryonic Development; Gene Expression Regulation, Developmental; Mammals; Mice; Protein Biosynthesis; RNA, Messenger, Stored; Zygote
PubMed: 35108058
DOI: 10.1126/sciadv.abj3967 -
Nature Jun 2023Translation regulation is critical for early mammalian embryonic development. However, previous studies had been restricted to bulk measurements, precluding precise...
Translation regulation is critical for early mammalian embryonic development. However, previous studies had been restricted to bulk measurements, precluding precise determination of translation regulation including allele-specific analyses. Here, to address this challenge, we developed a novel microfluidic isotachophoresis (ITP) approach, named RIBOsome profiling via ITP (Ribo-ITP), and characterized translation in single oocytes and embryos during early mouse development. We identified differential translation efficiency as a key mechanism regulating genes involved in centrosome organization and N-methyladenosine modification of RNAs. Our high-coverage measurements enabled, to our knowledge, the first analysis of allele-specific ribosome engagement in early development. These led to the discovery of stage-specific differential engagement of zygotic RNAs with ribosomes and reduced translation efficiency of transcripts exhibiting allele-biased expression. By integrating our measurements with proteomics data, we discovered that ribosome occupancy in germinal vesicle-stage oocytes is the predominant determinant of protein abundance in the zygote. The Ribo-ITP approach will enable numerous applications by providing high-coverage and high-resolution ribosome occupancy measurements from ultra-low input samples including single cells.
Topics: Animals; Mice; Protein Biosynthesis; Proteomics; Ribosomes; RNA, Messenger; Single-Cell Analysis; Embryonic Development; Alleles; Microfluidic Analytical Techniques; Oocytes; Isotachophoresis; Ribosome Profiling; Centrosome; Zygote
PubMed: 37344592
DOI: 10.1038/s41586-023-06228-9 -
The EMBO Journal Nov 2022Epigenome reprogramming after fertilization enables transcriptionally quiescent maternal and paternal chromatin to acquire a permissive state for subsequent zygotic...
Epigenome reprogramming after fertilization enables transcriptionally quiescent maternal and paternal chromatin to acquire a permissive state for subsequent zygotic genome activation (ZGA). H3K27 acetylation (H3K27ac) is a well-established chromatin marker of active enhancers and promoters. However, reprogramming dynamics of H3K27ac during maternal-to-zygotic transition (MZT) in mammalian embryos are not well-studied. By profiling the allelic landscape of H3K27ac during mouse MZT, we show that H3K27ac undergoes three waves of rapid global transitions between oocyte stage and 2-cell stage. Notably, germinal vesicle oocyte and zygote chromatin are globally hyperacetylated, with noncanonical, broad H3K27ac domains that correlate with broad H3K4 trimethylation (H3K4me3) and open chromatin. H3K27ac marks genomic regions primed for activation including ZGA genes, retrotransposons, and active alleles of imprinted genes. We show that CBP/p300 and HDAC activities play important roles in regulating H3K27ac dynamics and are essential for preimplantation development. Specifically, CBP/p300 acetyltransferase broadly deposits H3K27ac in zygotes to induce the opening of condensed chromatin at putative enhancers and ensure proper ZGA. On the contrary, HDACs revert broad H3K27ac domains to canonical domains and safeguard ZGA by preventing premature expression of developmental genes. In conclusion, coordinated activities of CBP/p300 and HDACs during mouse MZT are essential for ZGA and preimplantation development.
Topics: Mice; Animals; Zygote; Acetylation; Gene Expression Regulation, Developmental; Blastocyst; Chromatin; Mammals
PubMed: 36215692
DOI: 10.15252/embj.2022112012 -
Nature Genetics Apr 2021Polycomb repressive complexes 1 and 2 (PRC1/2) maintain transcriptional silencing of developmental genes largely by catalyzing the formation of mono-ubiquitinated...
Polycomb repressive complexes 1 and 2 (PRC1/2) maintain transcriptional silencing of developmental genes largely by catalyzing the formation of mono-ubiquitinated histone H2A at lysine 119 (H2AK119ub1) and trimethylated histone H3 at lysine 27 (H3K27me3), respectively. How Polycomb domains are reprogrammed during mammalian preimplantation development remains largely unclear. Here we show that, although H2AK119ub1 and H3K27me3 are highly colocalized in gametes, they undergo differential reprogramming dynamics following fertilization. H3K27me3 maintains thousands of maternally biased domains until the blastocyst stage, whereas maternally biased H2AK119ub1 distribution in zygotes is largely equalized at the two-cell stage. Notably, while maternal PRC2 depletion has a limited effect on global H2AK119ub1 in early embryos, it disrupts allelic H2AK119ub1 at H3K27me3 imprinting loci including Xist. By contrast, acute H2AK119ub1 depletion in zygotes does not affect H3K27me3 imprinting maintenance, at least by the four-cell stage. Importantly, loss of H2AK119ub1, but not H3K27me3, causes premature activation of developmental genes during zygotic genome activation (ZGA) and subsequent embryonic arrest. Thus, our study reveals distinct dynamics and functions of H3K27me3 and H2AK119ub1 in mouse preimplantation embryos.
Topics: Animals; Blastocyst; Epigenesis, Genetic; Female; Fertilization; Gene Expression Regulation, Developmental; Histones; Lysine; Male; Maternal Inheritance; Mice; Oocytes; Paternal Inheritance; Polycomb Repressive Complex 1; Polycomb Repressive Complex 2; Pregnancy; Protein Isoforms; RNA, Long Noncoding; Spermatozoa; Ubiquitination; Zygote
PubMed: 33821005
DOI: 10.1038/s41588-021-00821-2 -
Nature Jan 2024DNA replication enables genetic inheritance across the kingdoms of life. Replication occurs with a defined temporal order known as the replication timing (RT) programme,...
DNA replication enables genetic inheritance across the kingdoms of life. Replication occurs with a defined temporal order known as the replication timing (RT) programme, leading to organization of the genome into early- or late-replicating regions. RT is cell-type specific, is tightly linked to the three-dimensional nuclear organization of the genome and is considered an epigenetic fingerprint. In spite of its importance in maintaining the epigenome, the developmental regulation of RT in mammals in vivo has not been explored. Here, using single-cell Repli-seq, we generated genome-wide RT maps of mouse embryos from the zygote to the blastocyst stage. Our data show that RT is initially not well defined but becomes defined progressively from the 4-cell stage, coinciding with strengthening of the A and B compartments. We show that transcription contributes to the precision of the RT programme and that the difference in RT between the A and B compartments depends on RNA polymerase II at zygotic genome activation. Our data indicate that the establishment of nuclear organization precedes the acquisition of defined RT features and primes the partitioning of the genome into early- and late-replicating domains. Our work sheds light on the establishment of the epigenome at the beginning of mammalian development and reveals the organizing principles of genome organization.
Topics: Animals; Mice; Blastocyst; Chromatin; DNA Replication Timing; Epigenome; Genome; RNA Polymerase II; Zygote; Embryo, Mammalian
PubMed: 38123678
DOI: 10.1038/s41586-023-06872-1 -
Genes & Development May 2023Translation of maternal mRNAs is detected before transcription of zygotic genes and is essential for mammalian embryo development. How certain maternal mRNAs are...
Translation of maternal mRNAs is detected before transcription of zygotic genes and is essential for mammalian embryo development. How certain maternal mRNAs are selected for translation instead of degradation and how this burst of translation affects zygotic genome activation remain unknown. Using gene-edited mice, we document that the oocyte-specific eukaryotic translation initiation factor 4E family member 1b (eIF4E1b) is the regulator of maternal mRNA expression that ensures subsequent reprogramming of the zygotic genome. In oocytes, eIF4E1b binds to transcripts encoding translation machinery proteins, chromatin remodelers, and reprogramming factors to promote their translation in zygotes and protect them from degradation. The protein products are thought to establish an open chromatin landscape in one-cell zygotes to enable transcription of genes required for cleavage stage development. Our results define a program for rapid resetting of the zygotic epigenome that is regulated by maternal mRNA expression and provide new insights into the mammalian maternal-to-zygotic transition.
Topics: Animals; Mice; Embryonic Development; Gene Expression Regulation, Developmental; Oocytes; Protein Biosynthesis; RNA, Messenger, Stored; Zygote
PubMed: 37257918
DOI: 10.1101/gad.350400.123 -
The International Journal of... 2020Sexually reproducing organisms generate male and female haploid gametes, which meet and fuse at fertilization to produce a diploid zygote. The evolutionary process of... (Review)
Review
Sexually reproducing organisms generate male and female haploid gametes, which meet and fuse at fertilization to produce a diploid zygote. The evolutionary process of speciation is achieved and maintained by ensuring that gametes undergo productive fusion only within a species. In animals, hybrids from cross-species fertilization events may develop normally, but are usually sterile (Fitzpatrick, 2004). Metazoan sperm and eggs have several features to ensure that the gametes, which have evolved independently and also in conflict with each other, are competent to undergo fertilization (Firman, 2018). Fertilization is a specific process that is ideally supposed to result in randomized fusion of compatible egg and sperm. Here, I will discuss key processes driven by maternal factors in the egg that dictate earliest stages of gamete recognition, gamete choice and fusion in metazoans.
Topics: Animals; Biological Evolution; Female; Germ Cells; Male; Maternal Inheritance; Reproduction; Sperm-Ovum Interactions; Zygote
PubMed: 32659006
DOI: 10.1387/ijdb.190156sn