scholarly journals The miR-430 locus with extreme promoter density is a transcription body organizer, which facilitates long range regulation in zygotic genome activation

2021 ◽  
Author(s):  
Yavor Hadzhiev ◽  
Lucy Wheatley ◽  
Ledean Cooper ◽  
Federico Ansaloni ◽  
Celina Whalley ◽  
...  
Keyword(s):  
Rna Polymerase Ii ◽  
Gene Cluster ◽  
Core Promoter ◽  
Single Copy ◽  
Early Embryo ◽  
Zygotic Genome Activation ◽  
Pol Ii ◽  
A Minor ◽  
Genome Activation ◽  
Zygotic Genome

In anamniote embryos the major wave of zygotic genome activation (ZGA) starts during the mid-blastula transition. This major wave of ZGA is facilitated by several mechanisms, including dilution of repressive maternal factors and accumulation of activating transcription factors during the fast cell division cycles preceding the mid-blastula transition. However, a set of genes escape global genome repression and are activated substantially earlier, during what is called, the minor wave of genome activation. While the mechanisms underlying the major wave of genome activation have been studied extensively, the minor wave of genome activation is little understood. In zebrafish the earliest expressed RNA polymerase II (Pol II) transcribed genes are activated in a pair of large transcription bodies depleted of chromatin, abundant in elongating Pol II and nascent RNAs (Hadzhiev et al., 2019; Hilbert et al., 2021). This transcription body includes the miR-430 gene cluster required for maternal mRNA clearance. Here we explored the genomic, chromatin organisation and cis-regulatory mechanisms of the minor wave of genome activation occurring in the transcription body. By long read genome sequencing we identified a remarkable cluster of miR-430 genes with over 300 promoters and spanning 0.6 Mb, which represent the highest promoter density of the genome. We demonstrate that the miR-430 gene cluster is required for the formation of the transcription body and acts as a transcription organiser for minor wave activation of a set of zinc finger genes scattered on the same chromosome arm, which share promoter features with the miR-430 cluster. These promoter features are shared among minor wave genes overall and include the TATA-box and sharp transcription start site profile. Single copy miR-430 promoter transgene reporter experiments indicate the importance of promoter-autonomous mechanisms regulating escape from global repression of the early embryo. These results together suggest that formation of the transcription body in the early embryo is the result of high promoter density coupled to a minor wave-specific core promoter code for transcribing key minor wave ZGA genes, which are required for the overhaul of the transcriptome during early embryonic development.

scholarly journals Pleomorphic Adenoma Gene 1 Is Needed For Timely Zygotic Genome Activation and Early Embryo Development

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Elo Madissoon ◽  
Anastasios Damdimopoulos ◽  
Shintaro Katayama ◽  
Kaarel Krjutškov ◽  
Elisabet Einarsdottir ◽  
...  
Keyword(s):  
Pleomorphic Adenoma ◽  
Embryo Development ◽  
Early Embryo ◽  
Zygotic Genome Activation ◽  
Early Embryo Development ◽  
Genome Activation ◽  
Zygotic Genome

scholarly journals Histone variant H2A.Z regulates zygotic genome activation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Dafne Ibarra-Morales ◽  
Michael Rauer ◽  
Piergiuseppe Quarato ◽  
Leily Rabbani ◽  
Fides Zenk ◽  
...  
Keyword(s):  
Rna Polymerase Ii ◽  
De Novo ◽  
Housekeeping Genes ◽  
Histone Variant ◽  
Small Subset ◽  
Zygotic Genome Activation ◽  
Transcription Start Sites ◽  
Genome Activation ◽  
Zygotic Genome

AbstractDuring embryogenesis, the genome shifts from transcriptionally quiescent to extensively active in a process known as Zygotic Genome Activation (ZGA). In Drosophila, the pioneer factor Zelda is known to be essential for the progression of development; still, it regulates the activation of only a small subset of genes at ZGA. However, thousands of genes do not require Zelda, suggesting that other mechanisms exist. By conducting GRO-seq, HiC and ChIP-seq in Drosophila embryos, we demonstrate that up to 65% of zygotically activated genes are enriched for the histone variant H2A.Z. H2A.Z enrichment precedes ZGA and RNA Polymerase II loading onto chromatin. In vivo knockdown of maternally contributed Domino, a histone chaperone and ATPase, reduces H2A.Z deposition at transcription start sites, causes global downregulation of housekeeping genes at ZGA, and compromises the establishment of the 3D chromatin structure. We infer that H2A.Z is essential for the de novo establishment of transcriptional programs during ZGA via chromatin reorganization.

scholarly journals The Spatio-Temporal Control of Zygotic Genome Activation

2018 ◽  
Author(s):  
George E. Gentsch ◽  
Nick D. L. Owens ◽  
James C. Smith
Keyword(s):  
Cell Cycle ◽  
Rna Polymerase Ii ◽  
Temporal Dynamics ◽  
Bmp Signaling ◽  
Cycle Duration ◽  
Zygotic Genome Activation ◽  
Significant Events ◽  
Spatio Temporal ◽  
Genome Activation ◽  
Zygotic Genome

SUMMARYOne of the earliest and most significant events in embryonic development is zygotic genome activation (ZGA). In several species, bulk transcription begins at the mid-blastula transition (MBT) when, after a certain number of cleavages, the embryo attains a particular nuclear-to-cytoplasmic (N/C) ratio, maternal repressors become sufficiently diluted, and the cell cycle slows down. Here we resolve the frog ZGA in time and space by profiling RNA polymerase II (RNAPII) engagement and its transcriptional readout. We detect a gradual increase in both the quantity and the length of RNAPII elongation before the MBT, revealing that >1,000 zygotic genes disregard the N/C timer for their activation, and that the sizes of newly transcribed genes are not necessarily constrained by cell cycle duration. We also find that Wnt, Nodal and BMP signaling together generate most of the spatio-temporal dynamics of regional ZGA, directing the formation of orthogonal body axes and proportionate germ layers.

scholarly journals Chromatin accessibility established by Pou5f3, Sox19b and Nanog primes genes for activity during zebrafish genome activation

2019 ◽  
Author(s):  
Máté Pálfy ◽  
Gunnar Schulze ◽  
Eivind Valen ◽  
Nadine L. Vastenhouw
Keyword(s):  
Transcription Factors ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Regulatory Elements ◽  
Chromatin Accessibility ◽  
Zebrafish Genome ◽  
Zygotic Genome Activation ◽  
Lineage Specification ◽  
Genome Activation ◽  
Zygotic Genome

ABSTRACTIn many organisms, early embryonic development is driven by maternally provided factors until the controlled onset of transcription during zygotic genome activation. The regulation of chromatin accessibility and its relationship to gene activity during this transition remains poorly understood. Here, we generated chromatin accessibility maps from genome activation until the onset of lineage specification. During this period, chromatin accessibility increases at regulatory elements. This increase is independent of RNA polymerase II-mediated transcription, with the exception of the hyper-transcribed miR-430 locus. Instead, accessibility often precedes the transcription of associated genes. Loss of the maternal transcription factors Pou5f3, Sox19b, and Nanog, which are known to be required for zebrafish genome activation, results in decreased accessibility at regulatory elements. Importantly, the accessibility of regulatory regions, especially when established by Pou5f3, Sox19b and Nanog, is predictive for future transcription. Our results show that the maternally provided transcription factors Pou5f3, Sox19b, and Nanog open up chromatin and prime genes for activity during zygotic genome activation in zebrafish.

scholarly journals Wenshen Shengjing Decoction Improves Early Embryo Development by Maintaining Low H3K27me3 Levels in Sperm and Pronuclear Embryos of Spermatogenesis Impaired Mice

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Yanmei Sun ◽  
Fan Gao ◽  
Da Xu ◽  
Lei Lu ◽  
Qianggen Chen ◽  
...  
Keyword(s):  
Embryo Development ◽  
Early Embryo ◽  
Development Rate ◽  
Epigenetic Changes ◽  
Zygotic Genome Activation ◽  
Arrest Rate ◽  
Developmental Arrest ◽  
Early Embryos ◽  
Genome Activation ◽  
Zygotic Genome

Many ingredients in Wenshen Shengjing Decoction (WSSJD) can cause epigenetic changes in the development of different types of cells. It is not yet known whether they can cause epigenetic changes in sperms or early embryos. Here, we investigated the role of WSSJD in epigenetic modifications of sperms or early embryos and early embryo development. A mouse model with spermatogenesis disorders was established with cyclophosphamide (CPA). WSSJD was administrated for 30 days. The male model mice after the treatment were mated with the female mice treated with superovulation. The embryo development rate of each stage was calculated. Immunofluorescence staining was used to detect the expression of H3K27me3 in sperm, pronuclear embryos, and 2-cell embryos. Western blotting was used to detect the expression of histone demethylase KDM6A and methyltransferase EZH2 in 2-cell embryos with developmental arrest. The expressions of zygotic genome activation genes (ZSCAN4, E1F1AX, HSPA1A, ERV4-2, and MYC) in 2-cell embryos with developmental arrest were analyzed with qRT-PCR. Comparing with the control group, CPA destroyed the development of seminiferous epithelium, significantly increased the expression level of H3K27me3 in sperm, reduced the expression ratio of H3K27me3 in female and male pronuclei, delayed the development of 2-cell embryos, and increased the developmental arrest rate and degeneration rate of 2-cell embryos. Moreover, the expressions of EZH2 and H3K27me3 were significantly increased in the 2-cell embryos with developmental arrest, and the expression of zygotic genome activation genes (ZSCAN4, E1F1AX, HSPA1A, ERV4-2, and MYC) was significantly decreased. Compared with the CPA group, WSSJD promoted the development of seminiferous epithelium, maintained a low level of H3K27me3 modification in sperm and male pronucleus, significantly increased the development rate of 2-cell embryos and 3-4 cell embryos, and reduced the developmental arrest rate and degeneration rate of 2-cell embryos. WSSJD may promote early embryonic development by maintaining a low level of H3K27me3 modification in sperm and male pronucleus and regulating the zygotic genome activation in mice with spermatogenesis disorders induced by CPA.

scholarly journals DPPA2 and DPPA4 are necessary to establish a totipotent state in mouse embryonic stem cells

2018 ◽  
Author(s):  
Alberto De Iaco ◽  
Alexandre Coudray ◽  
Julien Duc ◽  
Didier Trono
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Chromatin Accessibility ◽  
Early Embryo ◽  
Zygotic Genome Activation ◽  
Cell Stage ◽  
Oocyte Expression ◽  
Genome Activation ◽  
Zygotic Genome

AbstractAfter fertilization of the transcriptionally silent oocyte, expression from both parental chromosomes is launched through so-called zygotic genome activation (ZGA), occurring in the mouse at the 2-cell stage. Amongst the first elements to be transcribed are the Dux gene, the product of which secondarily induces a wide array of ZGA genes, and a subset of evolutionary recent LINE-1 retrotransposons, which regulate chromatin accessibility in the early embryo. The maternally-inherited factors that activate Dux and LINE-1 transcription have so far remained unknown. Here we identify the paralog proteins DPPA2 and DPPA4 as responsible for this process.

scholarly journals Symmetrically dimethylated histone H3R2 promotes global transcription during minor zygotic genome activation in mouse pronuclei

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kohtaro Morita ◽  
Yuki Hatanaka ◽  
Shunya Ihashi ◽  
Masahide Asano ◽  
Kei Miyamoto ◽  
...  
Keyword(s):  
Rna Polymerase Ii ◽  
Arginine Methylation ◽  
Dna Demethylation ◽  
Zygotic Genome Activation ◽  
H3k4 Methylation ◽  
Cell Stage ◽  
Paternal Genome ◽  
Genome Activation ◽  
Histone Arginine Methylation ◽  
Zygotic Genome

AbstractPaternal genome reprogramming, such as protamine–histone exchange and global DNA demethylation, is crucial for the development of fertilised embryos. Previously, our study showed that one of histone arginine methylation, asymmetrically dimethylated histone H3R17 (H3R17me2a), is necessary for epigenetic reprogramming in the mouse paternal genome. However, roles of histone arginine methylation in reprogramming after fertilisation are still poorly understood. Here, we report that H3R2me2s promotes global transcription at the 1-cell stage, referred to as minor zygotic genome activation (ZGA). The inhibition of H3R2me2s by expressing a histone H3.3 mutant H3.3R2A prevented embryonic development from the 2-cell to 4-cell stages and significantly reduced global RNA synthesis and RNA polymerase II (Pol II) activity. Consistent with this result, the expression levels of MuERV-L as minor ZGA transcripts were decreased by forced expression of H3.3R2A. Furthermore, treatment with an inhibitor and co-injection of siRNA to PRMT5 and PRMT7 also resulted in the attenuation of transcriptional activities with reduction of H3R2me2s in the pronuclei of zygotes. Interestingly, impairment of H3K4 methylation by expression of H3.3K4M resulted in a decrease of H3R2me2s in male pronuclei. Our findings suggest that H3R2me2s together with H3K4 methylation is involved in global transcription during minor ZGA in mice.

scholarly journals Cohesin facilitates zygotic genome activation in zebrafish

2017 ◽  
Author(s):  
Michael Meier ◽  
Jenny Grant ◽  
Amy Dowdle ◽  
Amarni Thomas ◽  
Jennifer E. Gerton ◽  
...  
Keyword(s):  
Rna Polymerase Ii ◽  
Chromatin Structure ◽  
Cell Cycle Progression ◽  
Zygotic Genome Activation ◽  
Chromosome Architecture ◽  
Genome Wide ◽  
Pioneer Factor ◽  
Cohesin Subunit ◽  
Genome Activation ◽  
Zygotic Genome

At zygotic genome activation (ZGA), changes in chromatin structure are associated with new transcription immediately following the maternal-to-zygotic transition (MZT). The nuclear architectural proteins, cohesin and CCCTC-binding factor (CTCF), contribute to chromatin structure and gene regulation. We show here that normal cohesin function is important for ZGA in zebrafish. Depletion of cohesin subunit Rad21 delays ZGA without affecting cell cycle progression. In contrast, CTCF depletion has little effect on ZGA whereas complete abrogation is lethal. Genome wide analysis of Rad21 binding reveals a change in distribution from pericentromeric satellite DNA, and few locations including the miR-430 locus (whose products are responsible for maternal transcript degradation), to genes, as embryos progress through the MZT. After MZT, a subset of Rad21 binding occurs at genes dysregulated upon Rad21 depletion and overlaps pioneer factor Pou5f3, which activates early expressed genes. Rad21 depletion disrupts the formation of nucleoli and RNA polymerase II foci, suggestive of global defects in chromosome architecture. We propose that Rad21/cohesin redistribution to active areas of the genome is key to the establishment of chromosome organization and the embryonic developmental program.

scholarly journals RNA polymerase II interacts with the Hspa1b promoter in mouse epididymal spermatozoa

Reproduction ◽  
2009 ◽  
Vol 137 (6) ◽  
pp. 923-929 ◽  
Author(s):  
Donald C Wilkerson ◽  
Kevin D Sarge
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Cell Stage ◽  
Western Blots ◽  
Pol Ii ◽  
Epididymal Spermatozoa ◽  
The One ◽  
Genome Activation ◽  
Embryonic Viability ◽  
Zygotic Genome

TheHspa1b(Hsp70.1) gene is one of the first genes expressed after fertilization, with expression occurring during the minor zygotic genome activation (ZGA) in the absence of stress. This expression can take place in the male pronucleus as early as the one-cell stage of embryogenesis. The importance of HSPA1B for embryonic viability during times of stress is supported by studies showing that depletion of this protein results in a significant reduction in embryos developing to the blastocyte stage. Recently, we have begun addressing the mechanism responsible for allowing expression ofHspa1bduring the minor ZGA and found that heat shock transcription factor (HSF) 1 and 2 bind theHspa1bpromoter during late spermatogenesis. In this report, we have extended those studies using western blots and chromatin immunoprecipitation assays and found that RNA polymerase II (Pol II) is present in epididymal spermatozoa and bound to theHspa1bpromoter. These present results, in addition to our previous results, support a model in which the binding of HSF1, HSF2, SP1, and Pol II to the promoter ofHspa1bwould allow the rapid formation of a transcription-competent state during the minor ZGA, thereby allowingHspa1bexpression.

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