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Cold Spring Harbor Perspectives in... Nov 2015Epigenetic mechanisms play an essential role in the germline and imprinting cycle. Germ cells show extensive epigenetic programming in preparation for the generation of... (Review)
Review
Epigenetic mechanisms play an essential role in the germline and imprinting cycle. Germ cells show extensive epigenetic programming in preparation for the generation of the totipotent state, which in turn leads to the establishment of pluripotent cells in blastocysts. The latter are the cells from which pluripotent embryonic stem cells are derived and maintained in culture. Following blastocyst implantation, postimplantation epiblast cells develop, which give rise to all somatic cells as well as primordial germ cells, the precursors of sperm and eggs. Pluripotent stem cells in culture can be induced to undergo differentiation into somatic cells and germ cells in culture. Understanding the natural cycles of epigenetic reprogramming that occur in the germline will allow the generation of better and more versatile stem cells for both therapeutic and research purposes.
Topics: Adult Stem Cells; Animals; Blastocyst; Cell Communication; Cell Differentiation; DNA Methylation; Embryonic Development; Epigenomics; Genomic Imprinting; Histones; Oocytes; Pluripotent Stem Cells; Zygote
PubMed: 26525151
DOI: 10.1101/cshperspect.a019422 -
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 -
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 -
Cell Stem Cell Jun 20222-cell-like cells (2CLCs)-which comprise only ∼1% of murine embryonic stem cells (mESCs)-resemble blastomeres of 2-cell-stage embryos and are used to investigate...
2-cell-like cells (2CLCs)-which comprise only ∼1% of murine embryonic stem cells (mESCs)-resemble blastomeres of 2-cell-stage embryos and are used to investigate zygotic genome activation (ZGA). Here, we discovered that TRIM66 and DAX1 function together as negative regulators of the 2C-like state in mESCs. Chimeric assays confirmed that mESCs lacking TRIM66 or DAX1 function have bidirectional embryonic and extraembryonic differentiation potential. TRIM66 functions by recruiting the co-repressor DAX1 to the Dux promoter, and TRIM66's repressive effect on Dux is dependent on DAX1. A solved crystal structural shows that TRIM66's PHD finger recognizes H3K4-K9me3, and mutational evidence confirmed that TRIM66's PHD finger is essential for its repression of Dux. Thus, beyond expanding the scope of known 2CLC regulators, our study demonstrates that interventions disrupting TRIM66 or DAX1 function in mESCs yield 2CLCs with expanded bidirectional differentiation potential, opening doors for the practical application of these totipotent-like cells.
Topics: Animals; Embryonic Stem Cells; Gene Expression Regulation, Developmental; Genome; Mice; Promoter Regions, Genetic; Zygote
PubMed: 35659877
DOI: 10.1016/j.stem.2022.05.004 -
Clinical and Translational Medicine Dec 2022RNA modification-induced ovarian dysgenesis appears to be necessary for ovary development. However, how m C (5-methylcytosine)-coordinating modificatory transcripts are...
BACKGROUND
RNA modification-induced ovarian dysgenesis appears to be necessary for ovary development. However, how m C (5-methylcytosine)-coordinating modificatory transcripts are dynamically regulated during oogenesis, and ovarian development is unknown. The purpose of this study was to determine whether NOP2/Sun RNA methyltransferase 5 (Nsun5) deletion leads to suppression of ovarian function and arrest of embryonic development. The regulation of mRNA decay and stability by m C modification is essential at multiple stages during the maternal-to-zygotic (MZT) transition.
METHODS
Mouse ovaries and oocytes with Nsun5 and the KGN cell line were subjected to m C identification, alternative splicing analysis and protein expression. BS-m C-seq, real-time polymerase chain reaction, Western blot, immunofluorescence and actinomycin D treatment assays were used. In particular, BS-m C-seq revealed a dynamic pattern of m C sites and genes in the ovaries between Nsun5 and WT mice at the 2-month and 6-month stages. Diverse bioinformatic tools were employed to identify target genes for Nsun5.
RESULTS
Here, a maternal mRNA stability study showed that deletion of the m C methyltransferase Nsun5 obstructs follicular development and ovarian function, which leads directly to inhibition of embryogenesis and embryo development. Dynamic analysis of m C revealed that the level of m C decreased in a time-dependent manner after Nsun5 knockout. Regarding the molecular mechanism, we found that Nsun5 deficiency caused a m C decline in the exon and 3'UTR regions that influenced the translation efficiency of Mitotic arrest deficient 2 like 2 (MAD2L2) and Growth differentiation factor 9 (GDF9) in the ovary. Mechanistic investigation of alternative splicing indicated that Nsun5 triggers aberrant events in the exon region of Brd8.
CONCLUSIONS
Nsun5 loss arrests follicular genesis and development in ovarian aging, indicating that Nsun5/m C-regulated maternal mRNA stabilization is essential for MZT transition.
Topics: Pregnancy; Female; Mice; Animals; RNA, Messenger, Stored; Methyltransferases; RNA; Zygote; RNA Stability
PubMed: 36495115
DOI: 10.1002/ctm2.1137 -
Current Topics in Developmental Biology 2021The fertilized frog egg contains all the materials needed to initiate development of a new organism, including stored RNAs and proteins deposited during oogenesis, thus... (Review)
Review
The fertilized frog egg contains all the materials needed to initiate development of a new organism, including stored RNAs and proteins deposited during oogenesis, thus the earliest stages of development do not require transcription. The onset of transcription from the zygotic genome marks the first genetic switch activating the gene regulatory network that programs embryonic development. Zygotic genome activation occurs after an initial phase of transcriptional quiescence that continues until the midblastula stage, a period called the midblastula transition, which was first identified in Xenopus. Activation of transcription is programmed by maternally supplied factors and is regulated at multiple levels. A similar switch exists in most animals and is of great interest both to developmental biologists and to those interested in understanding nuclear reprogramming. Here we review in detail our knowledge on this major switch in transcription in Xenopus and place recent discoveries in the context of a decades old problem.
Topics: Animals; Genome; Oogenesis; Xenopus laevis; Zygote
PubMed: 34074529
DOI: 10.1016/bs.ctdb.2021.03.003 -
International Journal of Molecular... Oct 2016Fertilization is the fusion of the male and female gamete. The process involves the fusion of an oocyte with a sperm, creating a single diploid cell, the zygote, from... (Review)
Review
Fertilization is the fusion of the male and female gamete. The process involves the fusion of an oocyte with a sperm, creating a single diploid cell, the zygote, from which a new individual organism will develop. The elucidation of the molecular mechanisms of fertilization has fascinated researchers for many years. In this review, we focus on this intriguing process at the molecular level. Several molecules have been identified to play a key role in each step of this intriguing process (the sperm attraction from the oocyte, the sperm maturation, the sperm and oocyte fusion and the two gamete pronuclei fusion leading to the zygote). Understanding the molecular mechanisms of the cell‑cell interactions will provide a better understanding of the causes of fertility issues due to fertilization defects.
Topics: Animals; Female; Fertilization; Humans; Male; Oocytes; Spermatozoa; Zygote
PubMed: 27599669
DOI: 10.3892/ijmm.2016.2723