Maternal KLF17 regulates zygotic genome activation in the mouse
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE211845 | GEO | 2024/01/11
REPOSITORIES: GEO
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Project description:Vertebrate life begins with fertilization, then the zygote genome is activated after transient silencing, termed zygotic genome activation (ZGA). The mechanism of how ZGA initiates is far from clear although it underlay the mystery of totipotency and start of life. The specific property of the minor ZGA implied the possible critical role of ncRNA in the initiation of ZGA. Here we delineated the expression profile of the lncRNAs in the mouse early embryo development and elucidated their critical role in the minor ZGA. LncRNAs showed closer correlation with minor ZGA, they activated earlier than the protein coding genes (PCGs) and suppressed quickly after ZGA. H3K9me3 enrichment prior the ZGA could explain the suspended expression of major ZGA PCGs albeit they possess the PolII pre-configuration. The PolII enriched MuERV-L was found around the TSS of the minor ZGA lncRNAs, and they were responsible for the activation of the minor ZGA lncRNAs and the subsequent embryo development. Our work suggested the MuERV-L mediated minor ZGA lncRNA activation as a critical driver between the epigenetic reprogramming triggered by fertilization and the embryo developmental program, thus provided clues for understanding totipotency and starting of life.
2024-01-01 | GSE213407 | GEO
Project description:Zygotic genome activation (ZGA) marks the first transcription event in life, and human embryo developmental arrest has been highly correlated with ZGA failure in clinical studies. We utilized published single-cell RNA sequencing data and RNA-seq data to identify Trim75 is a potential driver of minor ZGA and may recruit EP300 and establish H3K27ac in the gene body of minor ZGA genes.
2023-03-20 | GSE227385 | GEO
Project description:The goal of the present study is to analyze the characteristics of maternal to zygotic transition (MZT) in Arabidopsis. The maternal-to-zygotic transition (MZT) is an essential developmental turning point during the alternation of generations in both plants and animals. In animals, early embryogenesis is maternally controlled and zygotic genome activation (ZGA) starts much later. However, in plants, the timing of MZT and parental contributions to the zygotic transcriptome remain unclear. To address above mentioned questions, we selected Arabidopsis as model plant for the analysis. Regarding to the characteristics of MZT, egg cells, embryos including spherical zygote, elongated zygote, 1-cell embryo and 32-cell embryo were isolated and collected for RNA sequencing. Hybrid zygotes at two representative stages from the reciprocal crosses between polymorphic Arabidopsis Columbia (Col) and Landsberg erecta (Ler) accessions were also sequenced for investigating the parental contributions. We demonstrate that plant MZT occurs during the zygote stage and is a two-step process, first involving rapid maternal transcript degradation and, second, large-scale de novo transcription. Parental contributions to the zygotic transcriptome are stage dependent over the course of zygote development; the spherical zygote is characterized by a maternally dominated transcriptome, whereas the elongated zygote genome shows equal parental contributions.
2019-05-12 | GSE121003 | GEO
Project description:During the maternal-to-zygotic transition (MZT), transcriptionally silent embryos rely on post-transcriptional regulation of maternal mRNAs until zygotic genome activation (ZGA). RNA-binding proteins (RBPs) are important regulators of post-transcriptional RNA processing events, yet their identities and functions during developmental transitions in vertebrates remain largely unexplored. Using mRNA interactome capture, we identified 227 RBPs in zebrafish embryos before and during ZGA, hereby named the zebrafish MZT mRNAbound proteome. This protein constellation consists of many conserved RBPs, with additional embryo- and stage-specific mRNA interactors that likely reflect the dynamics of RNA-protein interactions during MZT. The enrichment of numerous splicing factors like hnRNP proteins before ZGA was surprising, because maternal mRNAs were found to be fully spliced. To address potentially unique roles of RBPs in embryogenesis, we focused on hnRNP A1. iCLIP and subsequent mRNA reporter assays revealed a function for hnRNP A1 in the regulation of poly(A) tail length and translation of maternal mRNAs through sequence-specific association with 3’UTRs before ZGA. Comparison of iCLIP data from two developmental stages revealed that hnRNP A1 dissociates from maternal mRNAs at ZGA and instead regulates the nuclear processing of pri-miR-430 transcripts, which we validated experimentally. The shift from cytoplasmic to nuclear RNA targets was accompanied by a dramatic translocation of hnRNP A1 and other pre-mRNA splicing factors to the nucleus in a transcription-dependent manner. Thus, our study identifies global changes in RNA-protein interactions during vertebrate MZT and shows that hnRNP A1 RNA-binding activities are spatially and temporally coordinated to regulate RNA metabolism during early development.
2017-03-27 | PXD006098 | Pride
Project description:Upon fertilization, maternal factors direct development in a transcriptionally silent embryo. At the maternal-to-zygotic transition (MZT), a universal step in animal development, unknown maternal factors trigger zygotic genome activation (ZGA). In zebrafish, ZGA is required for gastrulation and clearance of maternal mRNAs, which is achieved in part by the conserved microRNA miR-430. However, the precise factors that activate the zygotic program remain largely unknown. Here we show that Nanog, Pou5f1 and SoxB1 are required for genome activation in zebrafish. We identified several hundred genes directly activated by maternal factors, thus constituting the first wave of zygotic transcription in zebrafish. Ribosome profiling in the pre-MZT embryo revealed that nanog, sox19b and pou5f1 are the most highly translated transcription factor mRNAs. Combined loss of function for Nanog, SoxB1 and Pou5f1 resulted in developmental arrest prior to gastrulation, and a failure to activate >75% of zygotic genes. Furthermore, we found that Nanog binds the miR-430 locus and together with Pou5f1 and SoxB1 initiate miR-430 expression and activity. Our results demonstrate that maternal Nanog, Pou5f1 and SoxB1 are required to initiate the zygotic developmental program and in turn trigger the clearance of the maternal program by activating miR-430 expression. Wild type and loss-of-function total mRNA sequencing of embryonic transcriptomes pre- and post-MZT; ribosome profiling pre-MZT
2013-09-22 | E-GEOD-47558 | biostudies-arrayexpress
Project description:Zebrafish embryos are transcriptional silent until activation of the zygotic genome during the 10th cell cycle. Onset of transcription is followed by cellular and morphological changes involving cell speciation and gastrulation. Previous genome-wide surveys of transcriptional changes only assessed gene expression levels; however, recent studies have shown the necessity to map isoform-specific transcriptional changes. Here we perform isoform discovery and quantification on transcriptome sequences from before and after zebrafish zygotic genome activation (ZGA). We identify novel isoforms and isoform switches during ZGA for genes related to cell adhesion, pluripotency and DNA methylation. Isoform switching events include alternative splicing and changes in transcriptional start sites and in 3’ untranslated regions. New isoforms are identified even for well-characterized genes such as pou5f1, sall4 and dnmt1. Genes involved in cell-cell interactions such as f11r and magi1 display isoform switches with alterations of coding sequences. We also detect over 1000 transcripts that acquire a longer 3’ terminal exon when transcribed zygotically relative to the maternal transcript counterparts. ChIP-seq data mapped onto skipped exon events reveals a correlation between histone H3K36trimethylation peaks and the skipped exons, suggesting epigenetic marks being part of alternative splicing regulation. The novel isoforms and isoform switches reported here include regulators of the transcriptional, cellular and morphological changes taking place around ZGA. Our data display an array of isoform-related functional changes and represent a valuable resource complementary to existing early embryo transcriptomes. Examination H3K36me3 in zebrafish whole embryos at the Post-MBT stage
2012-11-01 | E-GEOD-40629 | biostudies-arrayexpress
Project description:Maternal-to-zygotic transition (MZT) is a conserved and fundamental process during which the maternal environment of oocyte transits to the zygotic genome driven expression program, and terminally differentiated oocyte and sperm are reprogrammed to totipotency. Metaphase II (MII) oocytes and zygotes (one-cell embryo) serve as the mature oocyte and the initiation of pre-implantation embryo development respectively, and characterizing their molecular landscapes at protein levels plays an important role in uncovering MZT and zygotic genome activation (ZGA )in mammals. Here we used an ultrasensitive proteomic approach to depict an in-depth landscape for the very early stage of mouse MZT.
2023-05-23 | PXD041399 | Pride
Project description:The remodelling of the epigenome and transcriptome of the fertilised oocyte to establish totipotency in the zygote and developing embryo is one of the most critical processes in mammalian embryogenesis. Zygotic or embryonic genome activation (ZGA, EGA) in the 2-cell embryo in mouse, and the 8-cell embryo in humans, constitutes the first major wave of transcription. Failure to initiate ZGA leads to developmental defects, and contributes to the high attrition rates of human pre-implantation embryos. Due to limitations in cell numbers and experimental tractability, the mechanisms that regulate human embryonic genome activation in the totipotent embryo remain poorly understood. Here we report the discovery of human 8-cell like cells (8CLCs) specifically among naïve embryonic stem cells, but not primed pluripotent cells. 8CLCs express ZGA marker genes, such as ZSCAN4, LEUTX and DUXA, and their transcriptome closely resembles that of the 8-cell human embryo. 8-cell like cells reactivate 8-cell stage specific transposable elements such as HERVL and MLT2A1, and are characterized by upregulation of the methylation regulator DPPA3. 8CLCs show reduced SOX2 protein levels and can be identified based on expression of the novel protein marker TPRX1 in vitro. Overexpression of the transcription factor DUX4 not only increases ZGA-like transcription, but also enhances TPRX1+ 8CLCs formation. The discovery of 8CLCs provides a unique opportunity to model and manipulate human ZGA-like transcriptional programs in vitro, and will provide critical functional insights into one of the earliest events in human embryogenesis in vivo.
2022-02-23 | GSE178379 | GEO
Project description:Metabolic reprogramming of glucose and amino acids has been documented to affect early development. Here, we show that peroxisome-mediated β-oxidation is involved in lipids reprogramming to achieve H3K4me3 erasure and then zygotic genome activation (ZGA) in early embryo development. The metabolic patterns of fatty acids (FAs), triglyceride (TG) and phospholipid (PL) are reprogrammed during the oocyte-to-embryo transition. Very long-chain fatty acids (VLCFAs), arachidonic acid (ARA), phosphatidylethanolamine (PE), lysophosphatidylethanolamine (Lyso-PE), lysophosphatidylcholine (Lyso-PC), and methyl donors are stored in oocytes, and after fertilization, they are converted into phosphatidylcholine (PC) at the 2-cell stage. Mitochondrial β-oxidation prevails in oocytes, while peroxisomal β-oxidation plays a critical role in shortening the VLCFA to form TG and synthesize PC and balancing the ratio of saturated and unsaturated FAs, which consumes the methyl donors as conducive to H3K4me3 erasure at the 2-cell stage. Inhibiting the peroxisome-mediated β-oxidation disrupts lipids metabolism remodellingH3K4me3 erasure and subsequent ZGA, leading to embryo arrest at the 2-cell stage. Oocytes from obese mice show I a relatively low level of VLCFAs, defective peroxisomal β-oxidation, and incomplete H3K4me3 erasure and ZGA. Microinjection of two saturated fatty acids, palmitic and myristic acids, rescues 2-cell arrest caused by peroxisome-mediated β-oxidation inhibition and obesity, and overexpressing Pemt to consume the methyl donors has the same rescue effect. These results elucidate a novel link among the peroxisomal-β-oxidation-mediated lipid metabolism reprogramming, H3K4me3 modification and ZGA during oocyte-embryo transition, and may provide a unique approach to improve reproduction in obese women.
2023-09-07 | GSE242263 | GEO
Project description:Upon fertilization, the embryonic genome remains transcriptionally inactive until the mid-blastula transition. Zygotic genome activation (ZGA) of vertebrate embryos has been extensively studied using nucleic acid-based strategies, but proteomics data are still scarce, impeding the full mechanistic understanding of how ZGA is executed during the maternal-to-zygotic transition (MZT). Here, we performed quantitative proteomics to decipher the proteome landscape of zebrafish embryos during the MZT, quantifying nearly 5,000 proteins across four embryonic stages. The stage-specific clustering based on protein expression pattern revealed that helicases (i.e., eif4a2 and ruvbl1) facilitate pluripotency factors (i.e., nanog, pou5f3, ctcf, and hmga1) triggering ZGA in zebrafish, accompanied by the maternal product decay with P-bodies and ubiquitin dependent proteolytic pathway. Dozens of transcription factors show wave-like expression patterns during MZT, implying their diverse functions in triggering the ZGA and modulating differentiation for organ development. The combination of morpholino knockdown and quantitative proteomics demonstrated that maternal Nanog is required for proper embryogenesis by regulating 1) interactions with other pluripotency factors, 2) F-actin band formation, 3) cell cycle checkpoints and 4) maternal product degradation. This study represents the most systematic proteomics survey of developmentally regulated proteins and their expression profiles accompanying MZT in zebrafish, which is a valuable proteome resource for understanding ZGA.
2024-05-01 | PXD036678 | Pride