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Nature Structural & Molecular Biology May 2023Despite the significance of N-methyladenosine (mA) in gene regulation, the requirement for large amounts of RNA has hindered mA profiling in mammalian early embryos....
Despite the significance of N-methyladenosine (mA) in gene regulation, the requirement for large amounts of RNA has hindered mA profiling in mammalian early embryos. Here we apply low-input methyl RNA immunoprecipitation and sequencing to map mA in mouse oocytes and preimplantation embryos. We define the landscape of mA during the maternal-to-zygotic transition, including stage-specifically expressed transcription factors essential for cell fate determination. Both the maternally inherited transcripts to be degraded post fertilization and the zygotically activated genes during zygotic genome activation are widely marked by mA. In contrast to mA-marked zygotic ally-activated genes, mA-marked maternally inherited transcripts have a higher tendency to be targeted by microRNAs. Moreover, RNAs derived from retrotransposons, such as MTA that is maternally expressed and MERVL that is transcriptionally activated at the two-cell stage, are largely marked by mA. Our results provide a foundation for future studies exploring the regulatory roles of mA in mammalian early embryonic development.
Topics: Animals; Mice; Gene Expression Regulation, Developmental; Blastocyst; Oocytes; Embryonic Development; Zygote; MicroRNAs; Mammals
PubMed: 37081317
DOI: 10.1038/s41594-023-00969-x -
Cellular and Molecular Life Sciences :... Jan 2020Zygosis is the generation of new biological individuals by the sexual fusion of gamete cells. Our current understanding of eukaryotic phylogeny indicates that sex is... (Review)
Review
Zygosis is the generation of new biological individuals by the sexual fusion of gamete cells. Our current understanding of eukaryotic phylogeny indicates that sex is ancestral to all extant eukaryotes. Although sexual development is extremely diverse, common molecular elements have been retained. HAP2-GCS1, a protein that promotes the fusion of gamete cell membranes that is related in structure to certain viral fusogens, is conserved in many eukaryotic lineages, even though gametes vary considerably in form and behaviour between species. Similarly, although zygotes have dramatically different forms and fates in different organisms, diverse eukaryotes share a common developmental programme in which homeodomain-containing transcription factors play a central role. These common mechanistic elements suggest possible common evolutionary histories that, if correct, would have profound implications for our understanding of eukaryogenesis.
Topics: Animals; Biological Evolution; Cell Membrane; Eukaryota; Germ Cells; Phylogeny; Transcription Factors; Zygote
PubMed: 31203379
DOI: 10.1007/s00018-019-03187-1 -
Nature Communications Jul 2023Zygotic genome activation (ZGA) is essential for early embryonic development. However, the regulation of ZGA remains elusive in mammals. Here we report that a maternal...
Zygotic genome activation (ZGA) is essential for early embryonic development. However, the regulation of ZGA remains elusive in mammals. Here we report that a maternal factor TDP-43, a nuclear transactive response DNA-binding protein, regulates ZGA through RNA Pol II and is essential for mouse early embryogenesis. Maternal TDP-43 translocates from the cytoplasm into the nucleus at the early two-cell stage when minor to major ZGA transition occurs. Genetic deletion of maternal TDP-43 results in mouse early embryos arrested at the two-cell stage. TDP-43 co-occupies with RNA Pol II as large foci in the nucleus and also at the promoters of ZGA genes at the late two-cell stage. Biochemical evidence indicates that TDP-43 binds Polr2a and Cyclin T1. Depletion of maternal TDP-43 caused the loss of Pol II foci and reduced Pol II binding on chromatin at major ZGA genes, accompanied by defective ZGA. Collectively, our results suggest that maternal TDP-43 is critical for mouse early embryonic development, in part through facilitating the correct RNA Pol II configuration and zygotic genome activation.
Topics: Mice; Animals; RNA Polymerase II; Gene Expression Regulation, Developmental; Zygote; Embryonic Development; DNA-Binding Proteins; Mammals
PubMed: 37460529
DOI: 10.1038/s41467-023-39924-1 -
Nature Communications Aug 2023Somatic cell nuclear transfer (SCNT) can be used to reprogram differentiated somatic cells to a totipotent state but has poor efficiency in supporting full-term...
Somatic cell nuclear transfer (SCNT) can be used to reprogram differentiated somatic cells to a totipotent state but has poor efficiency in supporting full-term development. H3K9me3 is considered to be an epigenetic barrier to zygotic genomic activation in 2-cell SCNT embryos. However, the mechanism underlying the failure of H3K9me3 reprogramming during SCNT embryo development remains elusive. Here, we perform genome-wide profiling of H3K9me3 in cumulus cell-derived SCNT embryos. We find redundant H3K9me3 marks are closely related to defective minor zygotic genome activation. Moreover, SCNT blastocysts show severely indistinct lineage-specific H3K9me3 deposition. We identify MAX and MCRS1 as potential H3K9me3-related transcription factors and are essential for early embryogenesis. Overexpression of Max and Mcrs1 significantly benefits SCNT embryo development. Notably, MCRS1 partially rescues lineage-specific H3K9me3 allocation, and further improves the efficiency of full-term development. Importantly, our data confirm the conservation of deficient H3K9me3 differentiation in Sertoli cell-derived SCNT embryos, which may be regulated by alternative mechanisms.
Topics: Histones; Zygote; Nuclear Transfer Techniques; Embryonic Development; Blastocyst; Embryo, Mammalian; Cellular Reprogramming
PubMed: 37558707
DOI: 10.1038/s41467-023-40496-3 -
Development, Growth & Differentiation Dec 2022How the embryonic genome regulates accessibility to transcription factors is one of the major questions in understanding the spatial and temporal dynamics of gene... (Review)
Review
How the embryonic genome regulates accessibility to transcription factors is one of the major questions in understanding the spatial and temporal dynamics of gene expression during embryogenesis. Epigenomic analyses of embryonic chromatin provide molecular insights into cell-specific gene activities and genomic architectures. In recent years, significant advances have been made to elucidate the dynamic changes behind the activation of the zygotic genome in various model organisms. Here we provide an overview of the recent epigenomic studies pertaining to early Xenopus development.
Topics: Animals; Xenopus laevis; Epigenomics; Chromatin; Embryonic Development; Zygote; Gene Expression Regulation, Developmental
PubMed: 36168140
DOI: 10.1111/dgd.12813 -
Biology Open Dec 2021Mouse zygote morphokinetics were measured during interphase, the mitotic period, cytokinesis, and two-cell stage. Sequences of rounder-distorted-rounder shapes were...
Mouse zygote morphokinetics were measured during interphase, the mitotic period, cytokinesis, and two-cell stage. Sequences of rounder-distorted-rounder shapes were revealed, as were changing patterns of cross section area. A calcium chelator and an actin-disrupting agent inhibited the area changes that occurred between pronuclear envelope breakdown and cytokinesis. During cell division, two vortices developed in each nascent cell and they rotated in opposite directions at each end of the cell, a pattern that sometimes persisted for up to 10 h. Exchange with the environment may have been promoted by these shape and area cycles and persisting circulation in the cytoplasm may have a similar function between a cell's interior and periphery. Some of these movements were sporadically also seen in human zygotes with abnormal numbers of pronuclei and the two-cell stages that developed from these compromised human zygotes.
Topics: Animals; Cell Nucleus; Cytoplasm; Humans; Mice; Zygote
PubMed: 34935907
DOI: 10.1242/bio.059013 -
Current Topics in Developmental Biology 2020Mammalian embryogenesis depends on maternal factors accumulated in eggs prior to fertilization and on placental transfers later in gestation. In this review, we focus on... (Review)
Review
Mammalian embryogenesis depends on maternal factors accumulated in eggs prior to fertilization and on placental transfers later in gestation. In this review, we focus on initial events when the organism has insufficient newly synthesized embryonic factors to sustain development. These maternal factors regulate preimplantation embryogenesis both uniquely in pronuclear formation, genome reprogramming and cell fate determination and more universally in regulating cell division, transcription and RNA metabolism. Depletion, disruption or inappropriate persistence of maternal factors can result in developmental defects in early embryos. To better understand the origins of these maternal effects, we include oocyte maturation processes that are responsible for their production. We focus on recent publications and reference comprehensive reviews that include earlier scientific literature of early mouse development.
Topics: Animals; Embryo, Mammalian; Embryonic Development; Female; Gene Expression Regulation, Developmental; Genome; Maternal Inheritance; Mice; Oocytes; Zygote
PubMed: 32591079
DOI: 10.1016/bs.ctdb.2019.10.006 -
Current Opinion in Cell Biology Feb 2022The genome of an early embryo undergoes significant remodelling at the epigenetic, transcriptional, and structural levels. New technological developments have made it... (Review)
Review
The genome of an early embryo undergoes significant remodelling at the epigenetic, transcriptional, and structural levels. New technological developments have made it possible to study 3D genome organisation in the zygote and early embryo of many different species. Recent studies in human embryos, zebrafish, medaka, and Xenopus have revealed that, similar to previous results in mouse and Drosophila, the zygotic genome is unstructured prior to zygotic genome activation. While these studies show that topologically associating domains are established coincident with zygotic genome activation across species, other 3D genome structures have more varied timing. Here, we review recent studies examining the timing and mechanisms of establishment of 3D genome organisation in the early embryo, and discuss similarities and differences between species. Investigating the establishment of 3D chromatin conformation in early embryos has the potential to reveal novel mechanisms of 3D genome organisation.
Topics: Animals; Chromatin; Drosophila; Drosophila Proteins; Gene Expression Regulation, Developmental; Genome; Mice; Zebrafish; Zygote
PubMed: 35065445
DOI: 10.1016/j.ceb.2021.12.004 -
Biochemistry Dec 2019
Topics: Animals; Cell Lineage; Clustered Regularly Interspaced Short Palindromic Repeats; Male; Mice; RNA, Messenger; Single-Cell Analysis; Zygote
PubMed: 31730337
DOI: 10.1021/acs.biochem.9b00688 -
Current Opinion in Plant Biology Jun 2021Although flowering plants and mammals have distinct life cycles and developmental programs, epigenetic information in both plant and mammalian cells is faithfully... (Review)
Review
Although flowering plants and mammals have distinct life cycles and developmental programs, epigenetic information in both plant and mammalian cells is faithfully inherited across mitotic cell division. In mammals, epigenetic reprograming is a prominent process that is re-established in the zygote and germ line during early development. By contrast, plants do not produce germ cells until later in development. This difference, along with the many examples of the transmission of stable epialleles in plants, suggests that epigenetic reprograming in plants and mammals occurs via distinct mechanisms. In this review, we highlight recent advances in genome-wide epigenetic analyses in plants. These analyses provide insight into dynamic epigenetic regulation in plants and reveal unique processes that maintain genome integrity during plant sexual reproduction.
Topics: Animals; DNA Methylation; Epigenesis, Genetic; Genes, Plant; Plants; Reproduction; Zygote
PubMed: 33744743
DOI: 10.1016/j.pbi.2021.102032