Zygotic Genome Activation in Vertebrates

Abstract Embryonic patterning is critically dependent on zygotic genome activation (ZGA). In Drosophila melanogaster embryos, the pioneer factor Zelda directs ZGA, possibly in conjunction with other factors. Here we have explored novel involvement of Chromatin-Linked Adapter for MSL Proteins (CLAMP) during ZGA. CLAMP binds thousands of sites genome-wide throughout early embryogenesis. Interestingly, CLAMP relocates to target promoter sequences across the genome when ZGA is initiated. Although there is a considerable overlap between CLAMP and Zelda binding sites, the proteins display distinct temporal dynamics. To assess whether CLAMP occupancy affects gene expression, we analyzed transcriptomes of embryos zygotically compromised for either clamp or zelda and found that transcript levels of many zygotically-activated genes are similarly affected. Importantly, compromising either clamp or zelda disrupted the expression of critical segmentation and sex determination genes bound by CLAMP (and Zelda). Furthermore, clamp knockdown embryos recapitulate other phenotypes observed in Zelda-depleted embryos, including nuclear division defects, centrosome aberrations, and a disorganized actomyosin network. Based on these data, we propose that CLAMP acts in concert with Zelda to regulate early zygotic transcription.

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MouseXist expression begins at zygotic genome activation and is timed by a zygotic clock

Molecular Reproduction and Development ◽

10.1002/mrd.1126 ◽

2001 ◽

Vol 61 (1) ◽

pp. 14-20 ◽

Cited By ~ 54

Author(s):

Maurizio Zuccotti ◽

Michele Boiani ◽

Ruben Ponce ◽

Stefano Guizzardi ◽

Renato Scandroglio ◽

...

Keyword(s):

Zygotic Genome Activation ◽

Genome Activation ◽

Zygotic Genome

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Endodermal Maternal Transcription Factors Establish Super-Enhancers during Zygotic Genome Activation

Cell Reports ◽

10.1016/j.celrep.2019.05.013 ◽

2019 ◽

Vol 27 (10) ◽

pp. 2962-2977.e5 ◽

Cited By ~ 11

Author(s):

Kitt D. Paraiso ◽

Ira L. Blitz ◽

Masani Coley ◽

Jessica Cheung ◽

Norihiro Sudou ◽

...

Keyword(s):

Transcription Factors ◽

Zygotic Genome Activation ◽

Genome Activation ◽

Zygotic Genome

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Maternal Dppa2 and Dppa4 are dispensable for zygotic genome activation but important for offspring survival

Development ◽

10.1242/dev.200191 ◽

2021 ◽

Vol 148 (24) ◽

Author(s):

Oana Kubinyecz ◽

Fatima Santos ◽

Deborah Drage ◽

Wolf Reik ◽

Melanie A. Eckersley-Maslin

Keyword(s):

Null Allele ◽

Embryonic Stem ◽

Offspring Survival ◽

Zygotic Genome Activation ◽

Molecular Events ◽

Genome Activation ◽

Mitotic Chromatin ◽

Zygotic Genome

ABSTRACT Zygotic genome activation (ZGA) represents the initiation of transcription following fertilisation. Despite its importance, we know little of the molecular events that initiate mammalian ZGA in vivo. Recent in vitro studies in mouse embryonic stem cells have revealed developmental pluripotency associated 2 and 4 (Dppa2/4) as key regulators of ZGA-associated transcription. However, their roles in initiating ZGA in vivo remain unexplored. We reveal that Dppa2/4 proteins are present in the nucleus at all stages of preimplantation development and associate with mitotic chromatin. We generated conditional single and double maternal knockout mouse models to deplete maternal stores of Dppa2/4. Importantly, Dppa2/4 maternal knockout mice were fertile when mated with wild-type males. Immunofluorescence and transcriptome analyses of two-cell embryos revealed that, although ZGA took place, there were subtle defects in embryos that lacked maternal Dppa2/4. Strikingly, heterozygous offspring that inherited the null allele maternally had higher preweaning lethality than those that inherited the null allele paternally. Together, our results show that although Dppa2/4 are dispensable for ZGA transcription, maternal stores have an important role in offspring survival, potentially via epigenetic priming of developmental genes.

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A developmentally programmed splicing failure attenuates the DNA damage response during mammalian zygotic genome activation

10.1101/2020.11.25.397794 ◽

2020 ◽

Author(s):

Christopher D. R. Wyatt ◽

Barbara Pernaute ◽

André Gohr ◽

Marta Miret-Cuesta ◽

Lucia Goyeneche ◽

...

Keyword(s):

Dna Damage ◽

Dna Damage Response ◽

Transcriptional Control ◽

Exon Skipping ◽

Tissue Type ◽

Zygotic Genome Activation ◽

Damage Response ◽

Mammalian Embryos ◽

Genome Activation ◽

Zygotic Genome

ABSTRACTThe transition from maternal to embryonic transcriptional control is a crucial step in embryogenesis. However, how alternative splicing is regulated during this process and how it contributes to early development is unknown. Using transcriptomic data from pre-implantation stages of human, mouse and cow, we show that the stage of zygotic genome activation (ZGA) exhibits the highest levels of exon skipping diversity reported for any cell or tissue type. Interestingly, much of this exon skipping is temporary, leads to disruptive non-canonical isoforms, and occurs in genes enriched for DNA damage response in the three species. We identified two core spliceosomal components, Snrpb and Snrpd2, as regulators of these patterns. These genes have low maternal expression at the time of ZGA and increase sharply thereafter. Consistently, microinjection of Snrpb/d2 mRNA into mouse zygotes reduces the levels of temporary exon skipping at ZGA, and leads to an increase in etoposide-induced DNA damage response. Altogether, our results suggest that mammalian embryos undergo an evolutionarily conserved and developmentally programmed specific splicing failure at the time of genome activation that attenuates cellular responses to DNA damage at these early stages.

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Inhibition of DRP1 Impedes Zygotic Genome Activation and Preimplantation Development in Mice

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.788512 ◽

2021 ◽

Vol 9 ◽

Author(s):

Yuanyuan Li ◽

Ning-Hua Mei ◽

Gui-Ping Cheng ◽

Jing Yang ◽

Li-Quan Zhou

Keyword(s):

Embryo Development ◽

Preimplantation Embryo ◽

Preimplantation Embryos ◽

Dependent Manner ◽

Zygotic Genome Activation ◽

Preimplantation Embryo Development ◽

Cell Embryo ◽

Embryo Stage ◽

Genome Activation ◽

Zygotic Genome

Mitochondrion plays an indispensable role during preimplantation embryo development. Dynamic-related protein 1 (DRP1) is critical for mitochondrial fission and controls oocyte maturation. However, its role in preimplantation embryo development is still lacking. In this study, we demonstrate that inhibition of DRP1 activity by mitochondrial division inhibitor-1, a small molecule reported to specifically inhibit DRP1 activity, can cause severe developmental arrest of preimplantation embryos in a dose-dependent manner in mice. Meanwhile, DRP1 inhibition resulted in mitochondrial dysfunction including decreased mitochondrial activity, loss of mitochondrial membrane potential, reduced mitochondrial copy number and inadequate ATP by disrupting both expression and activity of DRP1 and mitochondrial complex assembly, leading to excessive ROS production, severe DNA damage and cell cycle arrest at 2-cell embryo stage. Furthermore, reduced transcriptional and translational activity and altered histone modifications in DRP1-inhibited embryos contributed to impeded zygotic genome activation, which prevented early embryos from efficient development beyond 2-cell embryo stage. These results show that DRP1 inhibition has potential cytotoxic effects on mammalian reproduction, and DRP1 inhibitor should be used with caution when it is applied to treat diseases. Additionally, this study improves our understanding of the crosstalk between mitochondrial metabolism and zygotic genome activation.

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