Similar Datasets
Project description:Zygotic genome activation (ZGA) is a complex process which denotes the initiation of gene expression after fertilization. Deciphering the proper timing and genes involved in ZGA program is still a fundamental challenge in early embryo development. Here, we present a new ZGA gene identification framework, named ZGA-Timer, based on the timecourse pattern from RNA-seq data. By performing ZGA-Timer and siRNA technology, we confirmed Uqcc3 as a novel ZGA gene in mice. As a unique feature of ZGA-Timer, time-series RNA-seq data are modeled by a pattern recognition method and the onset of ZGA can be estimated in multiple species. ZGA-Timer outperforms current foldchange-based approaches. Furthermore, we investigate the epigenetic modifications and find that accessible chromatin predominately contributes to the regulation of ZGA genes. Moreover, ZGA genes show significant enrichment in housekeeping genes and cancer driver genes. Together, our ZGA-Timer framework provides a new approach to further understand the ZGA process.
2021-05-18 | GSE174530 | GEO
Project description:Zygotic genome activation (ZGA) after fertilization is a conserved transcriptional activation process that enables the maternal-to-zygotic transition. However, the global view of ZGA, particularly at the initiation, is not yet completely understood. Here, we develop a method to capture and sequence newly synthesized RNA in the early mouse embryos, which provides a view of transcriptional reprogramming events during ZGA. Our data demonstrate that gene activation associated with major ZGA, previously thought to occur exclusively during the mid-to-late 2-cell stage, is already initiated in zygotes. Furthermore, we identify a set of genes activated during minor ZGA and observe an enrichment of the homeobox-containing Obox factor motif at the promoters of minor ZGA genes. Among several Obox factors, Obox3 overexpression in mouse embryonic stem cells activates ZGA genes. Notably, the expression of Obox3 is severely impaired in somatic cell nuclear transfer (SCNT) embryos, and restoring its expression corrects the ZGA profile and greatly improves SCNT embryo development. Hence, our study reveals the dynamic transcriptional reprogramming during ZGA and underscores the crucial role of Obox3 in facilitating totipotency acquisition.
2024-04-02 | GSE235547 | GEO
Project description:Zygotic genome activation (ZGA) is an impressed biological event following fertilization during early embryo development. Precise reprogramming of epigenetic modifications (e.g. histone H3 lysine 27 acetylation, H3K27ac) have been found contribute to safeguard ZGA in zebrafish and Drosophila, but the dynamic of H3K27ac and the underlying regulation mechanism in mammal embryos are still enigmatic yet. As the main erasers for histone acetylation, histone deacetylase 1 and 2 (HDAC1 and HDAC2) are reported essential for mouse oogenesis and embryo lineage development, while it is unclear if they are functional for ZGA. Here, we observed significant global decrease of H3K27ac during ZGA in both mouse and bovine embryos, and accumulation of HDAC1/2 is responsible for the decline of H3K27ac. Repression of HDAC1/2 by dominant negative mutation led to arrested development at late 2-cell stage in mouse embryos, accompanied by downregulation of genes supposed to be expressed during ZGA. ChIP-seq revealed abnormal distribution of H3K27ac, and DUX participates in H3K27ac aberrant hyper-acetylation in embryos overexpressed mutant HDAC1/2. Moreover, suppression of HDAC1/2 also restrains H3K4me3 removal at gene body regions via impeding expression of KDM5s during mouse ZGA, and compensatory exogenous Kdm5b mRNA can fix the exceeding H3K4me3 and failed ZGA. Intriguingly, function of HDAC1/2 seems to be conservative between mouse and bovine embryos. Together, this study reveals that HDAC1/2 is indispensable for mouse and bovine ZGA via regulating distribution of H3K27ac and H3K4me3.
2022-05-21 | GSE182554 | GEO
Project description:Zygotic genome activation (ZGA) is an impressed biological event following fertilization during early embryo development. Precise reprogramming of epigenetic modifications (e.g. histone H3 lysine 27 acetylation, H3K27ac) have been found contribute to safeguard ZGA in zebrafish and Drosophila, but the dynamic of H3K27ac and the underlying regulation mechanism in mammal embryos are still enigmatic yet. As the main erasers for histone acetylation, histone deacetylase 1 and 2 (HDAC1 and HDAC2) are reported essential for mouse oogenesis and embryo lineage development, while it is unclear if they are functional for ZGA. Here, we observed significant global decrease of H3K27ac during ZGA in both mouse and bovine embryos, and accumulation of HDAC1/2 is responsible for the decline of H3K27ac. Repression of HDAC1/2 by dominant negative mutation led to arrested development at late 2-cell stage in mouse embryos, accompanied by downregulation of genes supposed to be expressed during ZGA. ChIP-seq revealed abnormal distribution of H3K27ac, and DUX participates in H3K27ac aberrant hyper-acetylation in embryos overexpressed mutant HDAC1/2. Moreover, suppression of HDAC1/2 also restrains H3K4me3 removal at gene body regions via impeding expression of KDM5s during mouse ZGA, and compensatory exogenous Kdm5b mRNA can fix the exceeding H3K4me3 and failed ZGA. Intriguingly, function of HDAC1/2 seems to be conservative between mouse and bovine embryos. Together, this study reveals that HDAC1/2 is indispensable for mouse and bovine ZGA via regulating distribution of H3K27ac and H3K4me3.
2022-05-21 | GSE182553 | GEO
Project description:To investigate the function of nuclear pore complex (NPC) in the regulation of zygotic genome activation (ZGA), we microinjected medium dosage of WGA in zebrafish embryos at 1-cell stage to block NPC function. We then performed gene expression profiling analysis using data obtained from RNA-seq of control or WGA treated embryo at comparable developmental time point (4.3 hours post fertilization (hpf) ) or develomental stage (dome).
2023-02-22 | GSE212929 | GEO
Project description:To characterize the spatial patterns of zygtoic transcription during zygotic genome activation (ZGA) of Xenopus laevis embryos, we microinjected 5-ethynyl uridine (EU) into 1-cell stage embryos and isolated total RNAs from whole embryos at 5, 6, 7, 8 and 9 hours post-fertilization (hpf) at room temperature, respectively, covering the stages of pre-ZGA to widespread ZGA (stage 7-9). The animal pole (AP, ~ 1/3 at the top region of embryo) and the vegetal pole (VP,~ 1/3 at the bottom region of embryo) regions were dissected and used for total RNA isolation. To purify nascent transcripts, total RNAs were biotinylated using disulfide biotin azide via click reaction and biotinylated nascent transcripts were purified using streptavidin beads. Libraries were constructed from using the nascent transcripts. All libraries were sequenced on illumina NextSeq 500.
2022-08-22 | GSE201833 | GEO
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) is the first transcription event in life. However, it is unclear how RNA polymerase is engaged in initiating ZGA in mammals. Here, by developing small-scale Tn5-assisted chromatin cleavage with sequencing (Stacc–seq), we investigated the landscapes of RNA polymerase II (Pol II) binding in mouse embryos. We found that Pol II undergoes ‘loading’, ‘pre-configuration’, and ‘production’ during the transition from minor ZGA to major ZGA. After fertilization, Pol II is preferentially loaded to CG-rich promoters and accessible distal regions in one-cell embryos (loading), in part shaped by the inherited parental epigenome. Pol II then initiates relocation to future gene targets before genome activation (pre-configuration), where it later engages in full transcription elongation upon major ZGA (production). Pol II also maintains low poising at inactive promoters after major ZGA until the blastocyst stage, coinciding with the loss of promoter epigenetic silencing factors. Notably, inhibition of minor ZGA impairs the Pol II pre-configuration and embryonic development, accompanied by aberrant retention of Pol II and ectopic expression of one-cell targets upon major ZGA. Hence, step-wise transition of Pol II occurs when mammalian life begins, and minor ZGA has a key role in the pre-configuration of transcription machinery and chromatin for genome activation.
2020-10-28 | GSE135457 | GEO
Project description:Upon fertilization, drastic chromatin reorganization occurs during human preimplantation development. However, the global chromatin landscape and its molecular dynamics in this period remain largely unexplored. Deciphering such process is crucial for understanding both early human development and in vitro fertilization. Here, we investigated genome-wide chromatin accessibility in human preimplantation embryos by employing an improved ATAC-seq that uses as few as 20 cells. We found widespread accessible chromatin in early human embryos that overlaps extensively with putative cis-regulatory sequences and transposable elements. Integrative analyses showed both conservation and divergence in regulatory circuitry between human and mouse early development, and between naïve human pluripotency in vivo and human embryonic stem cells. Surprisingly, we also found widespread open chromatin at the 2-cell stage despite its minimal transcription activities. Such accessible chromatin loci are readily found at CpG-rich promoters. Unexpectedly, many others are located in distal regions enriched for transcription factor binding sites and overlap with partially methylated domains (PMDs) in human oocytes. A large portion of these regions then rapidly become inaccessible upon zygotic genome activation (ZGA). Importantly, such drastic transition of chromatin accessibility during ZGA is well conserved in mouse embryos. Furthermore, it strongly correlates with the reprogramming of non-canonical H3K4me3 (ncH3K4me3), a form of histone mark that is uniquely present in oocytes and pre-ZGA embryos and contributes to genome silencing. Finally, both the reprogramming of chromatin accessibility and ncH3K4me3 during ZGA is completely blocked upon transcription inhibition, indicating a critical role of zygotic transcription in shaping early epigenomes. Together, these data revealed conserved chromatin state transition during ZGA in human and mouse early development.
2018-05-03 | GSE101571 | 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