Journal articles on the topic 'ZGA'
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1
Mendelsohn, Colleen L., Craig E. Griffin, Wayne S. Rosenkrantz, Larry D. Brown, and Mona J. Boord. "Efficacy of Boric-Complexed Zinc and Acetic-Complexed Zinc Otic Preparations for Canine Yeast Otitis Externa." Journal of the American Animal Hospital Association 41, no. 1 (January 1, 2005): 12–21. http://dx.doi.org/10.5326/0410012.
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The purpose of this 2-week, double-blinded, controlled clinical trial was to evaluate the efficacy of topical amino acid-complexed zinc gluconate formulated with boric acid (ZGB) or acetic acid (ZGA) versus a topical placebo in the treatment of yeast otitis externa in dogs. Included in the study were dogs with otitis externa and a cytopathological finding of yeast organisms in the affected ear. Ears were treated with the placebo, ZGA, or ZGB medications. Yeast counts as well as clinical appearance of the ears were monitored. Results revealed that ZGB significantly reduced the number of yeast organisms in cases of otitis externa.
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Abe, Ken-ichiro, Satoshi Funaya, Dai Tsukioka, Machika Kawamura, Yutaka Suzuki, Masataka G. Suzuki, Richard M. Schultz, and Fugaku Aoki. "Minor zygotic gene activation is essential for mouse preimplantation development." Proceedings of the National Academy of Sciences 115, no. 29 (July 2, 2018): E6780—E6788. http://dx.doi.org/10.1073/pnas.1804309115.
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In mice, transcription initiates at the mid-one-cell stage and transcriptional activity dramatically increases during the two-cell stage, a process called zygotic gene activation (ZGA). Associated with ZGA is a marked change in the pattern of gene expression that occurs after the second round of DNA replication. To distinguish ZGA before and after the second-round DNA replication, the former and latter are called minor and major ZGA, respectively. Although major ZGA are required for development beyond the two-cell stage, the function of minor ZGA is not well understood. Transiently inhibiting minor ZGA with 5, 6-dichloro-1-β-d-ribofuranosyl-benzimidazole (DRB) resulted in the majority of embryos arresting at the two-cell stage and retention of the H3K4me3 mark that normally decreases. After release from DRB, at which time major ZGA normally occurred, transcription initiated with characteristics of minor ZGA but not major ZGA, although degradation of maternal mRNA normally occurred. Thus, ZGA occurs sequentially starting with minor ZGA that is critical for the maternal-to-zygotic transition.
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Deng, Mingtian, Baobao Chen, Zifei Liu, Yu Cai, Yongjie Wan, Jianguo Zhou, and Feng Wang. "Exchanges of histone methylation and variants during mouse zygotic genome activation." Zygote 28, no. 1 (November 20, 2019): 51–58. http://dx.doi.org/10.1017/s0967199419000649.
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SummaryMinor and major zygotic genome activation (ZGA) are crucial for preimplantation development. During this process, histone variants and methylation influence chromatin accessibility and consequently regulated the expression of zygotic genes. However, the detailed exchanges of these modifications during ZGA remain to be determined. In the present study, the epigenetic modifications of histone 3 on lysine 9 (H3K9), 27 (H3K27) and 36 (H3K36), as well as four histone variants were determined during minor and major ZGA and in post-ZGA stages of mouse embryos. Firstly, microH2A1, H3K27me3 and H3K36me3 were asymmetrically stained in the female pronucleus during minor ZGA but lost staining in major ZGA. Secondly, H3K9me2 and H3K9me3 were strongly stained in the female pronucleus, but weakly stained in the male pronucleus and disappeared after ZGA. Thirdly, H2A.Z and H3.3 were symmetrically stained in male and female pronuclei during minor ZGA. Moreover, H3K27me2 was not statistically changed during mouse early development, while H3K36me2 was only detected in 2- and 4-cell embryos. In conclusion, our data revealed dynamics of histone methylation and variants during mice ZGA and provided details of their exchange in mice embryogenesis. Moreover, we further inferred that macroH2A1, H2A.Z, H3K9me2/3 and H3K27me2/3 may play crucial roles during mouse ZGA.
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Lee, Hyeonji, Seong-Yeob You, Dong Wook Han, Hyeonwoo La, Chanhyeok Park, Seonho Yoo, Kiye Kang, Min-Hee Kang, Youngsok Choi, and Kwonho Hong. "Dynamic Change of R-Loop Implicates in the Regulation of Zygotic Genome Activation in Mouse." International Journal of Molecular Sciences 23, no. 22 (November 18, 2022): 14345. http://dx.doi.org/10.3390/ijms232214345.
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In mice, zygotic genome activation (ZGA) occurs in two steps: minor ZGA at the one–cell stage and major ZGA at the two–cell stage. Regarding the regulation of gene transcription, minor ZGA is known to have unique features, including a transcriptionally permissive state of chromatin and insufficient splicing processes. The molecular characteristics may originate from extremely open chromatin states in the one–cell stage zygotes, yet the precise underlying mechanism has not been well studied. Recently, the R-loop, a triple–stranded nucleic acid structure of the DNA/RNA hybrid, has been implicated in gene transcription and DNA replication. Therefore, in the present study, we examined the changes in R-loop dynamics during mouse zygotic development, and its roles in zygotic transcription or DNA replication. Our analysis revealed that R-loops persist in the genome of metaphase II oocytes and preimplantation embryos from the zygote to the blastocyst stage. In particular, zygotic R-loop levels dynamically change as development proceeds, showing that R-loop levels decrease as pronucleus maturation occurs. Mechanistically, R-loop dynamics are likely linked to ZGA, as inhibition of either DNA replication or transcription at the time of minor ZGA decreases R-loop levels in the pronuclei of zygotes. However, the induction of DNA damage by treatment with anticancer agents, including cisplatin or doxorubicin, does not elicit genome-wide changes in zygotic R-loop levels. Therefore, our study suggests that R-loop formation is mechanistically associated with the regulation of mouse ZGA, especially minor ZGA, by modulating gene transcription and DNA replication.
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Fu, Bo, Hong Ma, and Di Liu. "Functions and Regulation of Endogenous Retrovirus Elements during Zygotic Genome Activation: Implications for Improving Somatic Cell Nuclear Transfer Efficiency." Biomolecules 11, no. 6 (June 2, 2021): 829. http://dx.doi.org/10.3390/biom11060829.
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Endogenous retroviruses (ERVs), previously viewed as deleterious relics of ancestral retrovirus infections, are silenced in the vast majority of cells to minimize the risk of retrotransposition. Counterintuitively, bursts of ERV transcription usually occur during maternal-to-zygotic transition (MZT) in preimplantation embryos; this is regarded as a major landmark event in the zygotic genome activation (ZGA) process, indicating that ERVs play an active part in ZGA. Evolutionarily, the interaction between ERVs and hosts is mutually beneficial. The endogenization of retrovirus sequences rewires the gene regulatory network during ZGA, and ERV repression may lower germline fitness. Unfortunately, owing to various limitations of somatic cell nuclear transfer (SCNT) technology, both developmental arrest and ZGA abnormalities occur in a high percentage of cloned embryos, accompanied by ERV silencing, which may be caused by the activation failure of upstream ERV inducers. In this review, we discuss the functions and regulation of ERVs during the ZGA process and the feasibility of temporal control over ERVs in cloned embryos via exogenous double homeobox (DUX). We hypothesize that further accurate characterization of the ERV-rewired gene regulatory network during ZGA may provide a novel perspective on the development of preimplantation embryos.
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Wang, Xiangxiu, Wen Wang, Yiman Wang, Jia Chen, Guifen Liu, and Yong Zhang. "Antibody-free profiling of transcription factor occupancy during early embryogenesis by FitCUT&RUN." Genome Research 32, no. 2 (December 29, 2021): 378–88. http://dx.doi.org/10.1101/gr.275837.121.
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Key transcription factors (TFs) play critical roles in zygotic genome activation (ZGA) during early embryogenesis, whereas genome-wide occupancies of only a few factors have been profiled during ZGA due to the limitation of cell numbers or the lack of high-quality antibodies. Here, we present FitCUT&RUN, a modified CUT&RUN method, in which an Fc fragment of immunoglobulin G is used for tagging, to profile TF occupancy in an antibody-free manner and demonstrate its reliability and robustness using as few as 5000 K562 cells. We applied FitCUT&RUN to zebrafish undergoing embryogenesis to generate reliable occupancy profiles of three known activators of zebrafish ZGA: Nanog, Pou5f3, and Sox19b. By profiling the time-series occupancy of Nanog during zebrafish ZGA, we observed a clear trend toward a gradual increase in Nanog occupancy and found that Nanog occupancy prior to the major phase of ZGA is important for the activation of some early transcribed genes.
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Fu, Bo, Hong Ma, and Di Liu. "Endogenous Retroviruses Function as Gene Expression Regulatory Elements During Mammalian Pre-implantation Embryo Development." International Journal of Molecular Sciences 20, no. 3 (February 12, 2019): 790. http://dx.doi.org/10.3390/ijms20030790.
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Pre-implantation embryo development encompasses several key developmental events, especially the activation of zygotic genome activation (ZGA)-related genes. Endogenous retroviruses (ERVs), which are regarded as “deleterious genomic parasites”, were previously considered to be “junk DNA”. However, it is now known that ERVs, with limited conservatism across species, mediate conserved developmental processes (e.g., ZGA). Transcriptional activation of ERVs occurs during the transition from maternal control to zygotic genome control, signifying ZGA. ERVs are versatile participants in rewiring gene expression networks during epigenetic reprogramming. Particularly, a subtle balance exists between ERV activation and ERV repression in host–virus interplay, which leads to stage-specific ERV expression during pre-implantation embryo development. A large portion of somatic cell nuclear transfer (SCNT) embryos display developmental arrest and ZGA failure during pre-implantation embryo development. Furthermore, because of the close relationship between ERV activation and ZGA, exploring the regulatory mechanism underlying ERV activation may also shed more light on the enigma of SCNT embryo development in model animals.
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Bogolyubova, Irina, and Dmitry Bogolyubov. "An Immunocytochemical Study of Interchromatin Granule Clusters in Early Mouse Embryos." BioMed Research International 2013 (2013): 1–8. http://dx.doi.org/10.1155/2013/931564.
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Interchromatin granule clusters (IGCs) are universal nuclear domains. Their molecular composition and functions were studied in detail in somatic cells. Here, we studied IGCs in the nuclei of early mouse embryos during zygotic gene activation (ZGA). We found that the size of IGCs gradually increases during realization of ZGA events. Using immunocytochemical approaches, we showed that the molecular composition of IGCs is also modified in mouse embryos. The hyperphosphorylated form of RNA polymerase II and the transcription factor TFIID have been revealed in IGCs before the end of ZGA. Association of these factors with IGCs became more noticeable during ZGA realization. Our data suggest that IGCs in early mouse embryos have some functional peculiarities connected most probably with IGC formationde novo. We believe that IGCs in early mouse embryos not only are storage sites of splicing factors but also may be involved in mRNA metabolism and represent the multifunctional nuclear domains.
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Xu, Tengteng, Chengxue Liu, Mengya Zhang, Xin Wang, Yelian Yan, Qiuchen Liu, Yangyang Ma, et al. "Vitrification of Pronuclear Zygotes Perturbs Porcine Zygotic Genome Activation." Animals 12, no. 5 (February 28, 2022): 610. http://dx.doi.org/10.3390/ani12050610.
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Zygotic genome activation (ZGA) plays an essential role in early embryonic development. Vitrification is a common assisted reproductive technology that frequently reduces the developmental competence of embryos. However, the effect of vitrification on porcine ZGA and gene expression during ZGA remains largely unclear. Here, we found that vitrification of pronuclear zygotes derived from parthenogenetic activation (PA) and in vitro fertilization (IVF) resulted in a significant reduction in the rates of 2-cell, 4-cell, and blastocysts, but did not affect the quality of blastocysts. Functional research revealed that RNA polymerase II Inhibitor (α-amanitin) treatment significantly reduced global transcriptional activity and developmental efficiency of both 4-cell and 8-cell embryos, implying an essential role of ZGA in porcine early embryonic development. Furthermore, vitrification did not affect the synthesis of nascent mRNA of 2-cell embryos, but significantly inhibited global transcriptional activity of both 4-cell and 8-cell embryos, suggesting an impaired effect of vitrification on porcine ZGA. Correspondingly, the single-cell analysis showed that vitrification caused the downregulation or upregulation expression of maternal genes in 4-cell embryos, also significantly decreased the expression of zygotic genes. Taken together, these results indicated that vitrification of pronuclear zygotes impairs porcine zygotic genome activation.
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Tian, Jing Jing, Jun Fang Guan, Chun Jie Yan, Wen Chao Wang, Lin Qiang Hu, and Gang Cao. "Study on Treatment of Ammonia Nitrogen Waste Water by Zeolite-Granule-Adsorbent." Advanced Materials Research 668 (March 2013): 211–15. http://dx.doi.org/10.4028/www.scientific.net/amr.668.211.
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This paper focuses on the zeolite-granule-adsorbent(ZGA)’s efficiency of removing ammonium ion. The ZGA shows good performance with up to 73.41% for ammonium removal on the condition of ZGA loading 6g, contact time 6h, initial ammonium concentration 50 mg/L and pH=6. The adsorption kinetics is best approximated by the pseudo-second-order model, whereas the adsorption isotherm results indicated that Langmuir model provides the best fit for the equilibrium data. Furthermore, with regard to thermodynamic parameters, it was found that Gibbs free energy change (ΔG°) −19.31kJ/mol at T=298K, The negative data indicates the spontaneous nature of the adsorption process.
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Li, Xiangnan, Yueshi Liu, Qier Mu, Junliang Tian, and Haiquan Yu. "MiR-290 family maintains developmental potential by targeting p21 in mouse preimplantation embryos." Biology of Reproduction 106, no. 3 (December 14, 2021): 425–40. http://dx.doi.org/10.1093/biolre/ioab227.
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Abstract The miR-290 family is a mouse-specific microRNA cluster, which maintains mouse embryonic stem cells (ESCs) pluripotency by increasing OCT3/4 and C-MYC expression. However, its functions in mouse preimplantation embryos remain unclear, especially during zygotic genome activation (ZGA). In this study, miR-290 family expression increased from the two-cell embryo stage through the blastocyst stage. Inhibition of miR-294-3p/5p did not affect ZGA initiation or embryo development, whereas pri-miR-290 knockdown decreased ZGA gene expression and slowed embryonic development. In addition, pluripotency decreased in ESCs derived from pri-miR-290 knockdown blastocysts. To clarify the mechanism of action, 33 candidate miR-294-3p target genes were screened from three databases, and miR-294-3p directly targeted the 3′-untranslated region of Cdkn1a (p21) mRNA. Similar to pri-miR-290 knockdown, P21 overexpression impeded embryonic development, whereas simultaneous overexpression of P21 and pri-miR-290 partially rescued embryonic development. The results indicate that the miR-290 family participates in promoting ZGA process and maintaining developmental potency in embryos by targeting p21.
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Magnani, Luca, Christine M. Johnson, and Ryan A. Cabot. "Expression of eukaryotic elongation initiation factor 1A differentially marks zygotic genome activation in biparental and parthenogenetic porcine embryos and correlates with in vitro developmental potential." Reproduction, Fertility and Development 20, no. 7 (2008): 818. http://dx.doi.org/10.1071/rd08072.
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Zygotic genome activation (ZGA) is a major event during cleavage development. In vitro manipulation of mammalian embryos (including embryo culture) can result in developmental arrest around the time of ZGA. Eukaryotic elongation initiation factor 1A (eIF1A) has been used as a marker for ZGA in some mammalian species. We hypothesised expression of eIF1A can be used to assess ZGA in the pig; we also hypothesised that the expression profile of eIF1A can be used to assess developmental potential in vitro. The aims of the present study were to determine the expression pattern of eIF1A during porcine cleavage development and to assess its expression levels in embryos of different quality. We used a real-time reverse transcription–polymerase chain reaction assay to quantify eIF1A transcripts at different time points during cleavage development in porcine embryos produced by parthenogenetic activation (PA) and in vitro fertilisation (IVF). We found that eIF1A is activated at the two-cell stage in IVF embryos and at the four-cell stage in PA embryos. We showed that the increase in transcript levels observed in parthenogenetic embryos is dependent on de novo transcription. We found altered levels of eIF1A transcripts in parthenogenetic embryos that presented as either two- or eight-cell embryos 48 h after activation compared with four-cell embryos at the same time point. Our work supports the hypothesis that eIF1A is a marker of porcine ZGA and its expression profile can be used to assess embryo quality.
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Lefkopoulos, Stylianos. "Nuclear transport times ZGA onset." Nature Cell Biology 25, no. 1 (January 2023): 6. http://dx.doi.org/10.1038/s41556-022-01080-x.
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Liu, Yu, An Gang Lou, Shuo Yang, Zhong Shu Li, and Nan-Zhu Fang. "PSIV-B-38 Late-Breaking: Effect of Glutamate (Glu) on Developmental Block and the MZT Relative Genes Expression in Mouse embryo during in Vitro Culture." Journal of Animal Science 97, Supplement_3 (December 2019): 330–31. http://dx.doi.org/10.1093/jas/skz258.661.
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Abstract The risk of developmental block in mammal’s embryos is high during in vitro as compare to in vivo environment because the in vitro embryo-culture systems are suboptimal. During in vitro-culture the balance between ROS production and elimination is disturbed and may lead to 2-cell block in mouse embryos [1]. In the current study, we investigated the effects of Glu as anti-developmental block during IVC on ZGA and MZT on mouse embryos. The mouse embryos were divided into control and different level of Glu treated group. The cleavage rate was determined, the ROS and GSH level was investigated using DCHF-DA and CMF2HC respectively. The mRNA expression level of ZGA marker gene such as Eif-1α, Muerv l, Zscan4d and Hsp70.1 was analyzed among the groups using RT-PCR. The transition rate from 2-cell to 4-cell was significantly higher in 6mmol/L Glu treated group as compare to control and others treated groups. No significant difference was recorded in the level of ROS and GSH during MZT stage among the different groups. The mRNA expression level of ZGA marker gene was significantly increased at middle and late stage in 6mmol/L Glu treated group as compare to control and others treated groups. In conclusion, this study shows that the concentration of 6mmol/L Glu could maintain the dynamic balance of GSH and ROS, increase the expression of ZGA marker gene and maintain its high expression pattern of time series, directly participate in the ZGA activated process; ultimately reduce the risk of developmental block to ensure the successful completion of MZT. Reference [1] Lee MT, Bonneau AR, Giraldez AJ.Zygotic Genome Activation during the Maternal-to-Zygotic Transition. Annual Rev Cell Dev Biol [J], 2014, 30:581–613.
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Weivoda, Megan M., and Raymond J. Hohl. "Effects of Farnesyl Pyrophosphate Accumulation on Calvarial Osteoblast Differentiation." Endocrinology 152, no. 8 (May 17, 2011): 3113–22. http://dx.doi.org/10.1210/en.2011-0016.
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Statins, drugs commonly used to lower serum cholesterol, have been shown to stimulate osteoblast differentiation and bone formation. Statins inhibit 3-hydroxy-3-methylglutaryl (HMG)-coenzyme A reductase (HMGCR), the first step of the isoprenoid biosynthetic pathway, leading to the depletion of the isoprenoids farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP). The effects of statins on bone have previously been attributed to the depletion of GGPP, because the addition of exogenous GGPP prevented statin-stimulated osteoblast differentiation in vitro. However, in a recent report, we demonstrated that the specific depletion of GGPP did not stimulate but, in fact, inhibited osteoblast differentiation. This led us to hypothesize that isoprenoids upstream of GGPP play a role in the regulation of osteoblast differentiation. We demonstrate here that the expression of HMGCR and FPP synthase decreased during primary calvarial osteoblast differentiation, correlating with decreased FPP and GGPP levels during differentiation. Zaragozic acid (ZGA) inhibits the isoprenoid biosynthetic pathway enzyme squalene synthase, leading to an accumulation of the squalene synthase substrate FPP. ZGA treatment of calvarial osteoblasts led to a significant increase in intracellular FPP and resulted in inhibition of osteoblast differentiation as measured by osteoblastic gene expression, alkaline phosphatase activity, and matrix mineralization. Simultaneous HMGCR inhibition prevented the accumulation of FPP and restored osteoblast differentiation. In contrast, specifically inhibiting GGPPS to lower the ZGA-induced increase in GGPP did not restore osteoblast differentiation. The specificity of HMGCR inhibition to restore osteoblast differentiation of ZGA-treated cultures through the reduction in isoprenoid accumulation was confirmed with the addition of exogenous mevalonate. Similar to ZGA treatment, exogenous FPP inhibited the mineralization of primary calvarial osteoblasts. Interestingly, the effects of FPP accumulation on osteoblasts were found to be independent of protein farnesylation. Our findings are the first to demonstrate that the accumulation of FPP impairs osteoblast differentiation and suggests that the depletion of this isoprenoid may be necessary for normal and statin-induced bone formation.
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Wilkerson, Donald C., and Kevin D. Sarge. "RNA polymerase II interacts with the Hspa1b promoter in mouse epididymal spermatozoa." REPRODUCTION 137, no. 6 (June 2009): 923–29. http://dx.doi.org/10.1530/rep-09-0015.
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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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Low, Yixuan, Dennis Eng Kiat Tan, Zhenhua Hu, Shawn Ying Xuan Tan, and Wee-Wei Tee. "Transposable Element Dynamics and Regulation during Zygotic Genome Activation in Mammalian Embryos and Embryonic Stem Cell Model Systems." Stem Cells International 2021 (October 15, 2021): 1–17. http://dx.doi.org/10.1155/2021/1624669.
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Transposable elements (TEs) are mobile genetic sequences capable of duplicating and reintegrating at new regions within the genome. A growing body of evidence has demonstrated that these elements play important roles in host genome evolution, despite being traditionally viewed as parasitic elements. To prevent ectopic activation of TE transposition and transcription, they are epigenetically silenced in most somatic tissues. Intriguingly, a specific class of TEs—retrotransposons—is transiently expressed at discrete phases during mammalian development and has been linked to the establishment of totipotency during zygotic genome activation (ZGA). While mechanisms controlling TE regulation in somatic tissues have been extensively studied, the significance underlying the unique transcriptional reactivation of retrotransposons during ZGA is only beginning to be uncovered. In this review, we summarize the expression dynamics of key retrotransposons during ZGA, focusing on findings from in vivo totipotent embryos and in vitro totipotent-like embryonic stem cells (ESCs). We then dissect the functions of retrotransposons and discuss how their transcriptional activities are finetuned during early stages of mammalian development.
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Okada, Yuki, and Keisuke Aoshima. "KM mutant highlights enhancers in minor ZGA." Cell Cycle 14, no. 16 (July 17, 2015): 2541–42. http://dx.doi.org/10.1080/15384101.2015.1060774.
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Kim, Kyeoung-Hwa, You-Mi Seo, Eun-Young Kim, Su-Yeon Lee, Jini Kwon, Jung-Jae Ko, and Kyung-Ah Lee. "The miR-125 family is an important regulator of the expression and maintenance of maternal effect genes during preimplantational embryo development." Open Biology 6, no. 11 (November 2016): 160181. http://dx.doi.org/10.1098/rsob.160181.
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Previously, we reported that Sebox is a new maternal effect gene (MEG) that is required for early embryo development beyond the two-cell (2C) stage because this gene orchestrates the expression of important genes for zygotic genome activation (ZGA). However, regulators of Sebox expression remain unknown. Therefore, the objectives of the present study were to use bioinformatics tools to identify such regulatory microRNAs (miRNAs) and to determine the effects of the identified miRNAs on Sebox expression. Using computational algorithms, we identified a motif within the 3′UTR of Sebox mRNA that is specific to the seed region of the miR-125 family, which includes miR-125a-5p, miR-125b-5p and miR-351-5p. During our search for miRNAs, we found that the Lin28a 3′UTR also contains the same binding motif for the seed region of the miR-125 family. In addition, we confirmed that Lin28a also plays a role as a MEG and affects ZGA at the 2C stage, without affecting oocyte maturation or fertilization. Thus, we provide the first report indicating that the miR-125 family plays a crucial role in regulating MEGs related to the 2C block and in regulating ZGA through methods such as affecting Sebox and Lin28a in oocytes and embryos.
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Lima, C. A., V. Huntress, and E. W. Overström. "90 ENDOGENOUS MODIFICATIONS OF AURORA B AND AURORA C KINASE EXPRESSION IN MOUSE OOCYTES AND EARLY EMBRYOS." Reproduction, Fertility and Development 21, no. 1 (2009): 146. http://dx.doi.org/10.1071/rdv21n1ab90.
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The Aurora (Aur) proteins are a family of serine/threonine kinases that play fundamental roles in controlling M-phase progression. Previous reports have shown that AurB is vital for proper completion of karyokinesis and cytokinesis in somatic cells. The role of AurC in somatic cells has been found to be much less significant, whereas it appears to play an important role in spermatogenesis. The role of these Aur proteins is not well characterized in mouse oocytes and early embryos. The objective of this study was to assess changes of AurB and AurC mRNA and protein expression in mouse oocytes and early embryos as development progresses through the activation of the zygotic genome. Oocytes and embryos were collected from the oviducts of hormone-stimulated CF-1 mice. After culturing for varying amounts of time, cumulus-denuded samples were either fixed for immunofluorescence microscopy studies or lysed for analysis of mRNA levels through the use of reverse transcription-PCR (RT-PCR). Samples were processed for immunofluorescence using markers of spindle morphology (tubulin) and AurB. Analysis of relative levels of AurB and AurC mRNA were assessed by RT-PCR methods. Marked differences were observed in the localization of AurB when unfertilized oocytes or prezygotic genome activation (ZGA) embryos were compared with post-ZGA samples. There was no evidence of AurB protein localized to the mitotic spindle or resultant midbody in oocyte and early embryo samples. Embryos fixed post-ZGA demonstrated AurB localization, as is conventionally found in somatic cells. The AurB protein was found co-localized with DNA in metaphase stage blastomeres and associated with the midbody in blastomeres near completion of cytokinesis. Relative levels of AurB mRNA were not found to be significantly different when pre- and post-ZGA samples were compared. A significant decrease in relative levels of AurC mRNA was observed in fertilized pre-ZGA samples when compared with unfertilized oocyte counterparts. These observations demonstrate significant differences in the status of AurB and AurC mRNA levels and protein localization in mouse oocytes and early embryos when compared with somatic cells. Given earlier reports showing the vital role of AurC in spermatogenesis, the elevated levels of AurC mRNA observed in prefertilization oocytes may be indicative of a similar role of AurC during oogenesis. Elucidating temporal and localization details of Aur expression is vital to gaining further understanding of cell-cycle regulation in oogenesis and early embryogenesis.
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Rengaraj, Deivendran, Sohyoung Won, Jong Won Han, DongAhn Yoo, Heebal Kim, and Jae Yong Han. "Whole-Transcriptome Sequencing-Based Analysis of DAZL and Its Interacting Genes during Germ Cells Specification and Zygotic Genome Activation in Chickens." International Journal of Molecular Sciences 21, no. 21 (October 31, 2020): 8170. http://dx.doi.org/10.3390/ijms21218170.
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The deleted in azoospermia like (DAZL) is required for germ cells development and maintenance. In chickens, the mRNA and protein of DAZL, a representative maternally inherited germ plasm factor, are detected in the germ plasm of oocyte, zygote, and all stages of the intrauterine embryos. However, it is still insufficient to explain the origin and specification process of chicken germ cells, because the stage at which the zygotic transcription of DAZL occurs and the stage at which the maternal DAZL RNA/protein clears have not yet been fully identified. Moreover, a comprehensive understanding of the expression of DAZL interacting genes during the germ cells specification and development and zygotic genome activation (ZGA) is lacking in chickens. In this study, we identified a set of DAZL interacting genes in chickens using in silico prediction method. Then, we analyzed the whole-transcriptome sequencing (WTS)-based expression of DAZL and its interacting genes in the chicken oocyte, zygote, and Eyal-Giladi and Kochav (EGK) stage embryos (EGK.I to EGK.X). In the results, DAZL transcripts are increased in the zygote (onset of transcription), maintained the increased level until EGK.VI, and decreased from EGK.VIII (possible clearance of maternal RNAs). Among the DAZL interacting genes, most of them are increased either at 1st ZGA or 2nd ZGA, indicating their involvement in germ cells specification and development.
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Xia, Weikun, Jiawei Xu, Guang Yu, Guidong Yao, Kai Xu, Xueshan Ma, Nan Zhang, et al. "Resetting histone modifications during human parental-to-zygotic transition." Science 365, no. 6451 (July 4, 2019): 353–60. http://dx.doi.org/10.1126/science.aaw5118.
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Histone modifications regulate gene expression and development. To address how they are reprogrammed in human early development, we investigated key histone marks in human oocytes and early embryos. Unlike that in mouse oocytes, the permissive mark trimethylated histone H3 lysine 4 (H3K4me3) largely exhibits canonical patterns at promoters in human oocytes. After fertilization, prezygotic genome activation (pre-ZGA) embryos acquire permissive chromatin and widespread H3K4me3 in CpG-rich regulatory regions. By contrast, the repressive mark H3K27me3 undergoes global depletion. CpG-rich regulatory regions then resolve to either active or repressed states upon ZGA, followed by subsequent restoration of H3K27me3 at developmental genes. Finally, by combining chromatin and transcriptome maps, we revealed transcription circuitry and asymmetric H3K27me3 patterning during early lineage specification. Collectively, our data unveil a priming phase connecting human parental-to-zygotic epigenetic transition.
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Choi, I., and K. H. S. Campbell. "24 EFFECTS OF HISTONE METHYLATION RELATED GENES ON EPIGENETIC REPROGRAMMING AND ZYGOTIC GENE ACTIVATION IN OVINE SOMATIC CELL NUCLEAR TRANSFER (SCNT) EMBRYOS." Reproduction, Fertility and Development 21, no. 1 (2009): 112. http://dx.doi.org/10.1071/rdv21n1ab24.
Full textAbstract:
After fertilization, early embryo development is dependent upon maternally inherited proteins and protein synthesised from maternal mRNA until zygotic gene activation (ZGA) occurs. The transition of transcriptional activity from maternal to embryonic control occurs with the activation of rRNA genes and the formation of the nucleolus at the 8- to 16-cell stage that coincides with a prolonged fourth cell cycle in bovine and ovine embryos. However, previous studies have reported a shift in the longest cell cycle (fifth cell cycle) in bovine somatic cell nuclear transfer (SCNT) embryos, suggesting that the major genome activation is delayed, possibly due to incomplete changes in chromatin structure such as hypermethylation and hypoacetylation of histone (Memili and First 2000 Zygote 8, 87–96; Holm et al. 2003 Cloning Stem Cells 5, 133–142). Although global gene expression profile studies have been carried out in somatic cell nuclear transfer embryos, little is known about the expression of genes which can alter chromatin structure in early embryo development and possibly effect ZGA. To determine whether epigenetic reprogramming of donor nuclei affected ZGA and expression profiles in SCNT embryos, ZBTB33 (zinc finger and BTB domain containing 33, also known as kaiso, a methy-CpG specific repressor), BRG1(brahma-related gene 1, SWI/SNF family of the ATP-dependent chromatin remodeling complexes), JMJD1A (jumonji domain containing 1A, H3K9me2/1-specific demethylase), JMJD1C (putative H3K9-specific demethylase), and JMJD2C (H3K9me3-specific demethylase) were examined by RT-PCR at different developmental stages [germinal vesicle (GV), metaphase II (MII), 8- to 16-cell, 16- to 32-cell, and blastocyst in both parthenogenetic and SCNT embryos]. All genes were detected in parthenogenetic and SCNT blastocyts, and ZBTB33 was also expressed in all embryos at all stages tested. However, the onset of expression of JMJD1C, containing POU5F1 binding site at 5′-promoter region and BRG1 required for ZGA are delayed in SCNT embryos as compared to parthenotes (16- v. 8-cell, and blastoocyst v. 16-cell stage). Furthermore, JMJD2C containing NANOG binding sites at the 3′-flanking region was expressed in GV and MII oocytes and parthenogenetic blastocysts, whereas in SCNT embryos, JMJD2C was only observed from the 16-cell stage onwards. Interestingly, JMJD1A, which is positively regulated by POU5F1, was not detected in GV and MII oocytes but was present in blastocyst stage embryos of both groups. Taken together, these results suggest that incomplete epigenetic modifications of genomic DNA and histones lead to a delayed onset of ZGA which may affect further development and establishment of totipotency. Subsequently, aberrant expression patterns reported previously in SCNT embryos may be attributed to improper expression of histone H3K9 and H3K4 demethylase genes during early embryo development.
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Yogeswari, B., and R. Venkatesh. "Density Functional Theory Studies on Effects of Additive Hydration on Neutral and Zwitterionic Glycylalanine." SAMRIDDHI : A Journal of Physical Sciences, Engineering and Technology 13, SUP 2 (December 31, 2021): 320–34. http://dx.doi.org/10.18090/samriddhi.v13spli02.33.
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The density functional theory computations have been carried out to study the effect of stepwise hydration on the structures of various conformers of the Neutral Glycylalanine…(Water) n (NGA…(W) n ) (n=5-10) and Zwitterionic Glycylalanine...(Water) n (ZGA…(W)n) (n=5-9) clusters. This indicates that the most stable neural GA conformer is 50.2 kcal/mol lower in energy than its zwitterionic counterpart. The hydrogen bonding interaction energies with BSSE corrections have been analyzed. Starting from complexation with six water molecules, ZGA complexes turn out to be the most stable candidates than their neutral partners. Theories of Bader’s Atoms in Molecules (AIM) and Natural Bond Orbital (NBO) are applied to examine the hydrogen bonds in the solvated complexes. In all hydrated complexes, the N-H (amino group)-Ow and O15-H16… Ow bonds are observed to be relatively short and possess comparatively higher values of (r) and (r). A good correlation between the structural parameters and the properties of charge density is found.
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Zhang, Y. T., Y. Liu, and Z. Liu. "16 Improvement of porcine cloned embryo developmental competence via KDM4A overexpression and H3K9me3 methyltransferase inhibitor treatment." Reproduction, Fertility and Development 32, no. 2 (2020): 133. http://dx.doi.org/10.1071/rdv32n2ab16.
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Aberrant epigenetic reprogramming is a major reason for the developmental failure of somatic cell nuclear transfer (SCNT) embryos. Histone H3 lysine 9 trimethylation (H3K9me3), a histone marker for transcriptional repression, is considered a key barrier to the development of cloned embryos. In the present study, we found that H3K9me3 was much higher in SCNT embryos than in IVF embryos at the 4-cell and 2-cell stages; H3K9me3 demethylase KDM4A mRNA was injected into cloned embryos 5h after activation. The intensity of H3K9me3 modification decreased obviously after microinjection of KDM4A mRNA, and the developmental efficiency of porcine cloned embryos was enhanced significantly compared with control (32.2±4.2 vs. 21.0±3.5; P<0.05). Moreover, we evaluated the effect of chaetocin, an inhibitor of histone methyltransferase suv39h1/2, on SCNT embryo development. The results showed that 10 nM chaetocin not only suppressed the H3K9me3 modification in porcine embryonic fibroblast but also downregulated the expression of SUV39H1, SUV39H2, and KDM4D. However, treatment of cloned embryos with 10 nM chaetocin efficiently decreased the H3K9me3 level. Importantly, chaetocin treatment at the 4-cell stage for 6h significantly increased the blastocyst rate (57.8±4.3 vs. 43.5±1.8; P<0.05) compared with the control group. Furthermore, because a recent study showed that a high level of H3K9me3 appears in the reprogramming resistance region of nuclear transfer embryos during zygogene activation (ZGA), we examined the expression levels of ZGA-related genes. The qPCR results showed that the expression of ZGA-related genes increased significantly in SCNT embryos with chaetocin treatment compared with the control. These results suggested that chaetocin treatment can improve the efficiency of SCNT reprogramming during ZGA. In summary, our results suggested that H3K9me3 acts as an epigenetic barrier in porcine SCNT reprogramming and that a suv39h1/2 inhibitor can effectively reduce the H3K9me3 level in the early reprogramming phase and further improve the invitro developmental competence. Due to the existence of a variety of abnormal epigenetic mechanisms during somatic cell reprogramming, the combined use of small-molecule inhibitors is required in future studies. Data analyses were performed using SPSS software. Significance was set at P<0.05 unless otherwise specified. The results are expressed as the mean±standard deviation. This work was supported by the National Natural Science Foundation of China (grant number 31601942); the Postdoctoral Science Foundation of Heilongjiang Province (grant number LBH-Z17010); and the Fund for the National Key Research and Development program of China-Stem Cell and Translational Research (2016YFA0100200).
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Hao, Xiancai, Qian Wang, Jilun Hou, Kaiqiang Liu, Bo Feng, and Changwei Shao. "Temporal Transcriptome Analysis Reveals Dynamic Expression Profiles of Gametes and Embryonic Development in Japanese Flounder (Paralichthys olivaceus)." Genes 12, no. 10 (September 30, 2021): 1561. http://dx.doi.org/10.3390/genes12101561.
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The maternal-to-zygotic transition (MZT) is a crucial event in embryo development. While the features of the MZT across species are shared, the stage of this transition is different among species. We characterized MZT in a flatfish species, Japanese flounder (Paralichthys olivaceus). In this study, we analyzed the 551.57 GB transcriptome data of two types of gametes (sperms and eggs) and 10 embryo developmental stages in Japanese flounder. We identified 2512 maternal factor-related genes and found that most of those maternal factor-related genes expression decreased at the low blastula (LB) stage and remained silent in the subsequent embryonic development period. Meanwhile, we verified that the zygotic genome transcription might occur at the 128-cell stage and large-scale transcription began at the LB stage, which indicates the LB stage is the major wave zygotic genome activation (ZGA) occurs. In addition, we indicated that the Wnt signaling pathway, playing a diverse role in embryonic development, was involved in the ZGA and the axis formation. The results reported the list of the maternal genes in Japanese flounder and defined the stage of MZT, contributing to the understanding of the details of MZT during Japanese flounder embryonic development.
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Christians, E., E. Michel, P. Adenot, V. Mezger, M. Rallu, M. Morange, and J. P. Renard. "Evidence for the involvement of mouse heat shock factor 1 in the atypical expression of the HSP70.1 heat shock gene during mouse zygotic genome activation." Molecular and Cellular Biology 17, no. 2 (February 1997): 778–88. http://dx.doi.org/10.1128/mcb.17.2.778.
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The mouse HSP70.1 gene, which codes for a heat shock protein (hsp70), is highly transcribed at the onset of zygotic genome activation (ZGA). This expression, which occurs in the absence of stress, is then repressed. It has been claimed that this gene does not exhibit a stress response until the blastocyst stage. The promoter of HSP70.1 contains four heat shock element (HSE) boxes which are the binding sites of heat shock transcription factors (HSF). We have been studying the presence and localization of the mouse HSFs, mHSF1 and mHSF2, at different stages of embryo development. We show that mHSF1 is already present at the one-cell stage and concentrated in the nucleus. Moreover, by mutagenizing HSE sequences and performing competition experiments (in transgenic embryos with the HSP70.1 promoter inserted before a reporter gene), we show that, in contrast with previous findings, HSE boxes are involved in this spontaneous activation. Therefore, we suggest that HSF1 and HSE are important in this transient expression at the two-cell stage and that the absence of typical inducibility at this early stage of development results mainly from the high level of spontaneous transcription of this gene during the ZGA.
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Feng, Yun, Xin Zhao, Zhengda Li, Chan Luo, Ziyun Ruan, Jie Xu, Penglei Shen, et al. "Histone Demethylase KDM4D Could Improve the Developmental Competence of Buffalo (Bubalus Bubalis) Somatic Cell Nuclear Transfer (SCNT) Embryos." Microscopy and Microanalysis 27, no. 2 (January 22, 2021): 409–19. http://dx.doi.org/10.1017/s1431927620024964.
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AbstractSomatic cell nuclear transfer (SCNT) holds vast potential in agriculture. However, its applications are still limited by its low efficiency. Histone 3 lysine 9 trimethylation (H3K9me3) was identified as an epigenetic barrier for this. Histone demethylase KDM4D could regulate the level of H3K9me3. However, its effects on buffalo SCNT embryos are still unclear. Thus, we performed this study to explore the effects and underlying mechanism of KDM4D on buffalo SCNT embryos. The results revealed that compared with the IVF embryos, the expression level of KDM4D in SCNT embryos was significantly lower at 8- and 16-cell stage, while the level of H3K9me3 in SCNT embryos was significantly higher at 2-cell, 8-cell, and blastocyst stage. Microinjection of KDM4D mRNA could promote the developmental ability of buffalo SCNT embryos. Furthermore, the expression level of ZGA-related genes such as ZSCAN5B, SNAI1, eIF-3a, and TRC at the 8-cell stage was significantly increased. Meanwhile, the pluripotency-related genes like POU5F1, SOX2, and NANOG were also significantly promoted at the blastocyst stage. The results were reversed after KDM4D was inhibited. Altogether, these results revealed that KDM4D could correct the H3K9me3 level, increase the expression level of ZGA and pluripotency-related genes, and finally, promote the developmental competence of buffalo SCNT embryos.
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Quan, Hui, Hao Tian, Sirui Liu, Yue Xue, Yu Zhang, Wei Xie, and Yi Qin Gao. "Progressive Domain Segregation in Early Embryonic Development and Underlying Correlation to Genetic and Epigenetic Changes." Cells 10, no. 10 (September 23, 2021): 2521. http://dx.doi.org/10.3390/cells10102521.
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Chromatin undergoes drastic structural organization and epigenetic reprogramming during embryonic development. We present here a consistent view of the chromatin structural change, epigenetic reprogramming, and the corresponding sequence-dependence in both mouse and human embryo development. The two types of domains, identified earlier as forests (CGI-rich domains) and prairies (CGI-poor domains) based on the uneven distribution of CGI in the genome, become spatially segregated during embryonic development, with the exception of zygotic genome activation (ZGA) and implantation, at which point significant domain mixing occurs. Structural segregation largely coincides with DNA methylation and gene expression changes. Genes located in mixed prairie domains show proliferation and ectoderm differentiation-related function in ZGA and implantation, respectively. The chromatin of the ectoderm shows the weakest and the endoderm the strongest domain segregation in germ layers. This chromatin structure difference between different germ layers generally enlarges upon further differentiation. The systematic chromatin structure establishment and its sequence-based segregation strongly suggest the DNA sequence as a possible driving force for the establishment of chromatin 3D structures that profoundly affect the expression profile. Other possible factors correlated with or influencing chromatin structures, including transcription, the germ layers, and the cell cycle, are discussed for an understanding of concerted chromatin structure and epigenetic changes in development.
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Zhao, Long-Wen, Ye-Zhang Zhu, Yun-Wen Wu, Shuai-Bo Pi, Li Shen, and Heng-Yu Fan. "Nuclear poly(A) binding protein 1 (PABPN1) mediates zygotic genome activation-dependent maternal mRNA clearance during mouse early embryonic development." Nucleic Acids Research 50, no. 1 (December 14, 2021): 458–72. http://dx.doi.org/10.1093/nar/gkab1213.
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Abstract An embryo starts its life with maternal mRNA clearance, which is crucial for embryonic development. The elimination of maternal transcripts occurs by the joint action of two pathways: the maternally encoded mRNA decay pathway (M-decay) and the zygotic genome activation (ZGA)-dependent pathway (Z-decay). However, zygotic factors triggering maternal mRNA decay in early mammalian embryos remain largely unknown. In this study, we identified the zygotically encoded nuclear poly(A) binding protein 1 (PABPN1) as a factor required for maternal mRNA turnover, with a previously undescribed cytoplasmic function. Cytoplasmic PABPN1 docks on 3′-uridylated transcripts, downstream of terminal uridylyl transferases TUT4 and TUT7, and recruits 3′-5′ exoribonuclease DIS3L2 to its targets, facilitating maternal mRNA decay. Pabpn1-knockout in mice resulted in preimplantation stage mortality due to early developmental arrest at the morula stage. Maternal mRNAs to be eliminated via the Z-decay pathway failed to be removed from Pabpn1-depleted embryos. Furthermore, PABPN1-mediated Z-decay is essential for major ZGA and regulates the expression of cell fate-determining factors in mouse preimplantation embryos. This study revealed an unforeseen cytoplasmic function of PABPN1 coupled with early embryonic development, characterized the presence of a zygotic destabilizer of maternal mRNA, and elucidated the Z-decay process mechanisms, which potentially contribute to human fertility.
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Suzuki, T., N. Minami, and H. Imai. "89 ZYGOTICALLY ACTIVATED GENES ARE SUPPRESSED IN MOUSE NUCLEAR-TRANSFERRED EMBRYOS." Reproduction, Fertility and Development 19, no. 1 (2007): 162. http://dx.doi.org/10.1071/rdv19n1ab89.
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Mammalian oocytes have the ability to confer totipotency to terminally differentiated somatic cell nuclei. Viable cloned animals have been produced by somatic cell nuclear transfer (NT) into oocytes in many mammalian species including mouse. However, the success rates of the production were quite low in all species. Many studies have measured differences in gene expression between NT and fertilized embryos in relatively advanced stages of development such as pre- and post-natal stages or the blastocyst stage. In the mouse, major zygotic gene activation (ZGA) occurs at the 2-cell stage after fertilization and leads to the transition of gene regulation from maternal control to embryonic control. Suppression of the ZGA by a transcription inhibitor was shown to decrease the viability of embryos, and causes developmental arrest at the 2-cell stage. An abnormal ZGA may therefore affect the viability of NT embryos and cause further abnormalities in later embryonic development. In the present study, we compared gene expression patterns using differential display RT-PCR (DDRT-PCR) between the NT and IVF embryos at the 2-cell stage to detect some abnormalities affecting later development of NT embryos. The developmental rate of NT embryos to blastocysts (32.9%) was significantly lower than that of IVF (92.7%) or PA (92.8%). In addition, the cell numbers of NT embryos at the blastocyst stage (39.5 � 2.6; n = 19) were less than those of IVF (66.8 � 2.1; n = 30) or PA embryos (48.2 � 2.1; n = 30). Using these embryos, we first identified 4 genes that were differentially expressed between NT and IVF embryos at the 2-cell stage. Among the identified genes, Inpp5b and Chst12 were up-regulated, and MuERV-L and Dnaja2 were down-regulated in the NT embryos compared with IVF embryos. Further analysis showed that the expression of zygotically activated genes such as Interferon-γ, Dub-1, Spz1, DD2106, and DD2111 were not properly activated in NT embryos, suggesting that the cellular process involved in the control of the zygotic genome activation is not appropriately regulated. These results indicate that abnormal gene expression has already occurred at the early stage of pre-implantation development as a failure of nuclear reprogramming.
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Wu, Jingyi, Jiawei Xu, Bofeng Liu, Guidong Yao, Peizhe Wang, Zili Lin, Bo Huang, et al. "Chromatin analysis in human early development reveals epigenetic transition during ZGA." Nature 557, no. 7704 (May 2018): 256–60. http://dx.doi.org/10.1038/s41586-018-0080-8.
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QIU, Jia Jing, Wu Wen ZHANG, Zhi Li WU, Yi Hong WANG, Min QIAN, and Yi Ping LI. "Delay of ZGA initiation occurred in 2-cell blocked mouse embryos." Cell Research 13, no. 3 (June 2003): 179–85. http://dx.doi.org/10.1038/sj.cr.7290162.
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Syed, Sahla, Henry Wilky, João Raimundo, Bomyi Lim, and Amanda A. Amodeo. "The nuclear to cytoplasmic ratio directly regulates zygotic transcription inDrosophilathrough multiple modalities." Proceedings of the National Academy of Sciences 118, no. 14 (March 31, 2021): e2010210118. http://dx.doi.org/10.1073/pnas.2010210118.
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Early embryos must rapidly generate large numbers of cells to form an organism. Many species accomplish this through a series of rapid, reductive, and transcriptionally silent cleavage divisions. Previous work has demonstrated that the number of divisions before both cell cycle elongation and zygotic genome activation (ZGA) is regulated by the ratio of nuclear content to cytoplasm (N/C). To understand how the N/C ratio affects the timing of ZGA, we directly assayed the behavior of several previously identified N/C ratio–dependent genes using the MS2-MCP reporter system in livingDrosophilaembryos with altered ploidy and cell cycle durations. For every gene that we examined, we found that nascent RNA output per cycle is delayed in haploid embryos. Moreover, we found that the N/C ratio influences transcription through three overlapping modes of action. For some genes (knirps,fushi tarazu, andsnail), the effect of ploidy can be primarily attributed to changes in cell cycle duration. However, additional N/C ratio–mediated mechanisms contribute significantly to transcription delays for other genes. Forgiantandbottleneck,the kinetics of transcription activation are significantly disrupted in haploids, while forfrühstartandKrüppel, the N/C ratio controls the probability of transcription initiation. Our data demonstrate that the regulatory elements of N/C ratio–dependent genes respond directly to the N/C ratio through multiple modes of regulation.
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Sha, Qian-Qian, Ye-Zhang Zhu, Sen Li, Yu Jiang, Lu Chen, Xiao-Hong Sun, Li Shen, Xiang-Hong Ou, and Heng-Yu Fan. "Characterization of zygotic genome activation-dependent maternal mRNA clearance in mouse." Nucleic Acids Research 48, no. 2 (November 28, 2019): 879–94. http://dx.doi.org/10.1093/nar/gkz1111.
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Abstract An important event of the maternal-to-zygotic transition (MZT) in animal embryos is the elimination of a subset of the maternal transcripts that accumulated during oogenesis. In both invertebrates and vertebrates, a maternally encoded mRNA decay pathway (M-decay) acts before zygotic genome activation (ZGA) while a second pathway, which requires zygotic transcription, subsequently clears additional mRNAs (Z-decay). To date the mechanisms that activate the Z-decay pathway in mammalian early embryos have not been investigated. Here, we identify murine maternal transcripts that are degraded after ZGA and show that inhibition of de novo transcription stabilizes these mRNAs in mouse embryos. We show that YAP1-TEAD4 transcription factor-mediated transcription is essential for Z-decay in mouse embryos and that TEAD4-triggered zygotic expression of terminal uridylyltransferases TUT4 and TUT7 and mRNA 3′-oligouridylation direct Z-decay. Components of the M-decay pathway, including BTG4 and the CCR4-NOT deadenylase, continue to function in Z-decay but require reinforcement from the zygotic factors for timely removal of maternal mRNAs. A long 3′-UTR and active translation confer resistance of Z-decay transcripts to M-decay during oocyte meiotic maturation. The Z-decay pathway is required for mouse embryo development beyond the four-cell stage and contributes to the developmental competence of preimplantation embryos.
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Zhang, Zhiren, Yanhui Zhai, Xiaoling Ma, Sheng Zhang, Xinglan An, Hao Yu, and Ziyi Li. "Down-Regulation of H3K4me3 by MM-102 Facilitates Epigenetic Reprogramming of Porcine Somatic Cell Nuclear Transfer Embryos." Cellular Physiology and Biochemistry 45, no. 4 (2018): 1529–40. http://dx.doi.org/10.1159/000487579.
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Background/Aims: Aberrantly high levels of H3K4me3, caused by incomplete epigenetic reprogramming, likely cause a low efficiency of somatic cell nuclear transfer (SCNT). Smal molecule inhibitors aimed at epigenetic modification can be used to improve porcine SCNT embryo development. In this study, we examined the effects of MM-102, an H3K4 histone methyltransferase inhibitor, on porcine SCNT preimplantation embryos to investigate the mechanism by which H3K4 methylation regulated global epigenetic reprograming during SCNT. Methods: MM-102 was added to the SCNT embryos culture system and the global levels of various epigenetic modifications were measured by immunofluorescence (IF) staining and were quantified by Image J software. Relative genes expression levels were detected by quantitative real-time PCR. Results: MM-102 (75 μM) treatment reduced global H3K4, H3K9 methylation and 5mC levels especially at the zygotic gene activation (ZGA) and blastocyst stages. MM-102 treatment mainly down-regulated a series of DNA and histone methyltransferases, and up-regulated a number of hitone acetyltransferases and transcriptional activators. Furthermore, MM-102 treatment positively regulated the mRNA expression of genes related to pluripotency (OCT4, NANOG, CDX2) and apoptosis (BCL2). Conclusion: Down-regulation of H3K4me3 with MM-102 rescued aberrant gene expression patterns of a series of epigenetic chromatin modification enzymes, pluripotent and apoptotic genes at the ZGA and blastocyst stages, thereby greatly improving porcine SCNT efficiency and blastocyst quality, making them more similar to in vivo embryos (IVV).
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Khangura, Ravjit K., Martin J. Barbetti, and Mark W. Sweetingham. "Characterization and Pathogenicity of Rhizoctonia Species on Canola." Plant Disease 83, no. 8 (August 1999): 714–21. http://dx.doi.org/10.1094/pdis.1999.83.8.714.
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A total of 112 Rhizoctonia isolates were collected from various canola (Brassica napus) growing areas of Western Australia. Pectic enzyme electrophoresis differentiated these isolates into six distinct zymogram groups: R. solani, 54% ZG5 (AG2-1), 8% ZG6 (AG2-1), and 1% ZG9 (AG10); binucleate Rhizoctonia, 12% CZG1 (CAG1), 4% CZG4, and 6% CZG5 (AGK); and the remainder unidentified binucleate groups (15%). Binucleate groups were also confirmed by fluorescent nuclear staining and hyphal morphology. One or more isolates from each of the above zymogram groups (including four unidentified binucleate groups) and an isolate of ZG1-1 (AG8) that causes bare patch in cereals and legumes were tested for their pathogenicity on canola. Isolates of ZG5 and ZG1-1 were highly pathogenic on canola, delayed seedling emergence, and caused severe hypocotyl and root rot, respectively. ZG5 also induced postemergence damping-off. Increasing the depth of sowing from 1 to 3 cm significantly delayed seedling emergence and increased disease severity. Four unidentified binucleate isolates (WAC9316, WAC9297, WAC9307, and WAC9290) were moderately pathogenic to canola, while two isolates (WAC9307 and WAC9316) caused significant preemergence damping-off. Two CZG5 isolates were weakly pathogenic. Isolates of ZG5 and ZG1-1 were also tested for their pathogenicity on other rotational crops (narrow-leafed lupin, subterranean clover, wheat, oats, barley, and mustard) and two weed species (wild radish and annual ryegrass). ZG5 caused a severe hypocotyl rot on mustard and mild symptoms of hypocotyl rot on narrow-leafed lupin and clover, but failed to infect any of the cereal hosts, such as wheat, oats, barley, and ryegrass. In contrast, all crops tested were highly susceptible to ZG1-1 except mustard, which was only moderately susceptible. Results indicate that ZG5 is most pathogenic to crucifers and is a mildly virulent pathogen of the leguminous crops but not of cereal crops tested. ZG1-1, known to cause bare patch in legumes and cereals, also can cause severe root rot in canola. This is the first report of hypocotyl rot and pathogenicity of ZG5 on canola in Australia.
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Shin, S., K. Matsumoto, T. Amano, K. Saeki, Y. Hosoi, and A. Iritani. "281 EXPRESSION PROFILE AND KNOCKDOWN ANALYSIS OF A FUNCTIONALLY UNKNOWN DD2-2 GENE IN MOUSE PRE-IMPLANTATION EMBRYOS." Reproduction, Fertility and Development 19, no. 1 (2007): 256. http://dx.doi.org/10.1071/rdv19n1ab281.
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Zygotic gene activation (ZGA) starts at the G2 phase at the 1-cell stage in the mouse. However, the molecular mechanism of ZGA has not been completely elucidated. We have investigated the molecular functions of many gene clusters, DD clones obtained by differential display assays for ovulated eggs at the M II stage and 1-cell stage embryos at the G2 phase. As a result, we have identified a functionally unknown gene, whose sequence did not match a known transcript in the gene bank DD2-2 gene. Here, we report the expression profile and knockdown analysis of the DD2-2 gene in mouse pre-implantation embryos. Nucleotide sequence analysis of the DD2-2 cDNA revealed that the open reading frame of 1056 bp encodes a protein of 351 amino acids with a predicted molecular mass of 41.5 kDa. The deduced amino acid sequence indicated that DD2-2 protein might be a soluble protein without a signal peptide. We first investigated the expression profiles of DD2-2 in pre-implantation embryos by quantitative real-time PCR using an ABI PRISM 7300 Sequence Detection System (Applied Biosystems, Foster City, CA, USA). To investigate the effect of knockdown of the DD2-2 gene on the development of pre-implantation embryos, we injected pβ-act/antisenseDD2-2/IRES/EGFP into male pronuclei of embryos at 7 to 9 h after insemination (hpi) and observed the development of embryos that showed EGFP expression at 24 hpi. Real-time PCR analysis of pre-implantation embryos showed that maternal DD2-2 mRNA at a low level significantly increased up to the early 2-cell stage, and significantly decreased by the 4-cell stage and later, suggesting that DD2-2 gene specifically expresses at major ZGA. In the knockdown analysis, EGFP-positive embryos with pβ-act/antisenseDD2-2/IRES/EGFP showed a lower rate of development to the 4-cell stage and later, compared with that of EGFP-positive embryos with pβ-act/luc+/IRES/EGFP [72% (94/130) vs. 54% (71/131); P < 0.05], indicating that the knockdown of DD2-2 by antisense RNA resulted in a inhibition of pre-implantation development. In conclusion, the DD2-2 gene, a functionally unknown gene, may play an important role in pre-implantation development. This study was supported by a Grant-in-Aid for the 21st Century COE Program of the Japan Mext and by a grant for the Wakayama Prefecture Collaboration of Regional Entities for the Advancement of Technology Excellence of the JST.
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Wu, Jingyi, Jiawei Xu, Bofeng Liu, Guidong Yao, Peizhe Wang, Zili Lin, Bo Huang, et al. "Publisher Correction: Chromatin analysis in human early development reveals epigenetic transition during ZGA." Nature 560, no. 7718 (June 20, 2018): E27. http://dx.doi.org/10.1038/s41586-018-0267-z.
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Liu, Bofeng, Qianhua Xu, Qiujun Wang, Su Feng, Fangnong Lai, Peizhe Wang, Fangyuan Zheng, et al. "The landscape of RNA Pol II binding reveals a stepwise transition during ZGA." Nature 587, no. 7832 (October 28, 2020): 139–44. http://dx.doi.org/10.1038/s41586-020-2847-y.
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Zhu, Hou Quan, Rui Ming Fang, and Chang Qing Peng. "Parameter Identification for Power Transformer Using Zooming Genetic Algorithms." Advanced Materials Research 860-863 (December 2013): 2149–52. http://dx.doi.org/10.4028/www.scientific.net/amr.860-863.2149.
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Transfer functions of power transformer can be used for detection and localization of partial discharges. There is no access to sectional windings when transformer insulation has been impregnated into oil, so the parameter identification of transformer windings is difficult without the knowledge of sectional winding voltages. In this paper, genetic algorithms (GAs) based approach are proposed to identify the parameters of transformer windings. An impulse signal was injected into the bushings of transformer, then the responses at neutral terminals were measured, and thee acquired data were used to identify the parameters using GAs. To accelerate GAs’ convergence, a zooming operator was introduced in genetic programming process. The experimental results show that the proposed ZGA approach is effective.
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Rosół, Rafał. "“The Messengers are Called Sangandai”: the Greek σαγγάνδης and its Relationship to ἀσγάνδης/ ἀστάνδης." Philologia Classica 16, no. 1 (2021): 40–49. http://dx.doi.org/10.21638/spbu20.2021.104.
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This article examines the Greek noun σαγγάνδης ‘messenger’ which is attested in two lexica, dated to the Roman or early Byzantine periods: the Cambridge Rhetorical Lexicon by an anonymous author and Difficult Words in the Attic Orators by Claudius Casilo. In both works, σαγγάνδης appears together with three words of likely Iranian provenance: ὀροσάγγης ‘benefactor of the Persian king; bodyguard’, παρασάγγης ‘parasang; messenger’ and ἄγγαρος ‘messenger, courier; workman, labourer’. The word σαγγάνδης is analysed in comparison with ἀσγάνδης/ ἀστάνδης ‘messenger’ occurring for the first time in Plutarch’s works and closely linked to the Achaemenid administration. According to the hypothesis put forward in the present paper, both σαγγάνδης and σγάνδης (with its secondary variant στάνδης) are connected to Manichaean Middle Persian/Parthian ižgand ‘messenger’, Sogdian (a)žγand/(ɔ) žγand/ž(i)γant ‘id.’, Jewish Aramaic ʾîzgaddā ‘id.’, Syriac izgandā/izgaddā ‘id.’, Mandaic ašganda ‘helper, assistant, servant; the Messenger’, and go back to Old Persian *zganda- or to early Middle Persian/early Parthian *žgand- (or *zgand-) with the original meaning ‘mounted messenger’. The reconstructed noun is derived from the Proto-Iranian root *zga(n)d- ‘to go on, gallop, mount’, attested in Avestan (Younger Avestan zgaδ(/θ)- ‘to go on horseback, gallop’) and in some Middle and Modern Iranian languages. The original form of the loanword in Greek was probably *σγάνδης which then underwent certain transformations.
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Ren, Wei, Leilei Gao, Yaling Mou, Wen Deng, Jinlian Hua, and Fan Yang. "DUX: One Transcription Factor Controls 2-Cell-like Fate." International Journal of Molecular Sciences 23, no. 4 (February 13, 2022): 2067. http://dx.doi.org/10.3390/ijms23042067.
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The double homeobox (Dux) gene, encoding a double homeobox transcription factor, is one of the key drivers of totipotency in mice. Recent studies showed Dux was temporally expressed at the 2-cell stage and acted as a transcriptional activator during zygotic genome activation (ZGA) in embryos. A similar activation occurs in mouse embryonic stem cells, giving rise to 2-cell-like cells (2CLCs). Though the molecular mechanism underlying this expanded 2CLC potency caused by Dux activation has been partially revealed, the regulation mechanisms controlling Dux expression remain elusive. Here, we discuss the latest advancements in the multiple levels of regulation of Dux expression, as well as Dux function in 2CLCs transition, aiming to provide a theoretical framework for understanding the mechanisms that regulate totipotency.
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Zhang, Ke, Dan-Ya Wu, Hui Zheng, Yao Wang, Qiao-Ran Sun, Xin Liu, Li-Yan Wang, et al. "Analysis of Genome Architecture during SCNT Reveals a Role of Cohesin in Impeding Minor ZGA." Molecular Cell 79, no. 2 (July 2020): 234–50. http://dx.doi.org/10.1016/j.molcel.2020.06.001.
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Srinivasan, Rajini, Nataliya Nady, Neha Arora, Laura J. Hsieh, Tomek Swigut, Geeta J. Narlikar, Mark Wossidlo, and Joanna Wysocka. "Zscan4 binds nucleosomal microsatellite DNA and protects mouse two-cell embryos from DNA damage." Science Advances 6, no. 12 (March 2020): eaaz9115. http://dx.doi.org/10.1126/sciadv.aaz9115.
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Zinc finger protein Zscan4 is selectively expressed in mouse two-cell (2C) embryos undergoing zygotic genome activation (ZGA) and in a rare subpopulation of embryonic stem cells with 2C-like features. Here, we show that Zscan4 specifically recognizes a subset of (CA)n microsatellites, repeat sequences prone to genomic instability. Zscan4-associated microsatellite regions are characterized by low nuclease sensitivity and high histone occupancy. In vitro, Zscan4 binds nucleosomes and protects them from disassembly upon torsional strain. Furthermore, Zscan4 depletion leads to elevated DNA damage in 2C mouse embryos in a transcription-dependent manner. Together, our results identify Zscan4 as a DNA sequence–dependent microsatellite binding factor and suggest a developmentally regulated mechanism, which protects fragile genomic regions from DNA damage at a time of embryogenesis associated with high transcriptional burden and genomic stress.
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SHIN, Seung-Wook, Mikiko TOKORO, Satoshi NISHIKAWA, Hyang-Heun LEE, Yuki HATANAKA, Takuji NISHIHARA, Tomoko AMANO, et al. "Inhibition of the Ubiquitin-proteasome System Leads to Delay of the Onset of ZGA Gene Expression." Journal of Reproduction and Development 56, no. 6 (2010): 655–63. http://dx.doi.org/10.1262/jrd.10-104m.
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Kudasov, Yu B., M. V. Logunov, R. V. Kozabaranov, I. V. Makarov, V. V. Platonov, O. M. Surdin, D. A. Maslov, et al. "Giant widening of interface magnetic layer in almost compensated iron garnet." Applied Physics Letters 120, no. 12 (March 21, 2022): 122403. http://dx.doi.org/10.1063/5.0086067.
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A two-sublattice ferrimagnet undergoes a transition from a collinear to the canted magnetic phase at magnetic field oriented along an easy magnetization direction. In this work, we study the transition by means of the magneto-optical Faraday effect in a thin film of compensated iron garnet (Lu3− xBi x)(Fe5− y−zGa yAl z)O12 grown on the Gd3Ga5O12 substrate. In the immediate vicinity of the compensation temperature, a precursor of the transition with a complex shape was observed. Using a special sample with variable thickness, we demonstrate an interfacial origin of the precursor. Diffusion of gadolinium from the substrate into the film forms a thin intermixed layer with enhanced magnetization. It induces an extended inhomogeneous magnetic structure in the film. A two-step shape of the precursor appears due to an easy-plane anisotropy of the intermixed magnetic layer. We emphasize that an effective width of the inhomogeneous magnetization distribution in the film grows enormously while approaching the compensation temperature.
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Zhou, Congcong, Zhongying Qian, Qian Ji, Hui Xu, Lili Chen, Xiuqing Luo, Liang Min, Kexuan Tang, Jianbo Xiao, and Guoyin Kai. "Expression of the zga agglutinin gene in tobacco can enhance its anti-pest ability for peach-potato aphid (Myzus persica)." Acta Physiologiae Plantarum 33, no. 5 (February 4, 2011): 2003–10. http://dx.doi.org/10.1007/s11738-011-0715-y.
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Huang, Xin, Xiaohan Tang, Xuemei Bai, Honglei Li, Huan Tao, Junting Wang, Yaru Li, et al. "dbEmbryo multi-omics database for analyses of synergistic regulation in early mammalian embryo development." Genome Research 32, no. 8 (August 2022): 1612–25. http://dx.doi.org/10.1101/gr.276744.122.
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During early mammalian embryo development, different epigenetic marks undergo reprogramming and play crucial roles in the mediation of gene expression. Currently, several databases provide multi-omics information on early embryos. However, how interconnected epigenetic markers function together to coordinate the expression of the genetic code in a spatiotemporal manner remains difficult to analyze, markedly limiting scientific and clinical research. Here, we present dbEmbryo, an integrated and interactive multi-omics database for human and mouse early embryos. dbEmbryo integrates data on gene expression, DNA methylation, histone modifications, chromatin accessibility, and higher-order chromatin structure profiles for human and mouse early embryos. It incorporates customized analysis tools, such as “multi-omics visualization,” “Gene&Peak annotation,” “ZGA gene cluster,” “cis-regulation,” “synergistic regulation,” “promoter signal enrichment,” and “3D genome.” Users can retrieve gene expression and epigenetic profile patterns to analyze synergistic changes across different early embryo developmental stages. We showed the uniqueness of dbEmbryo among extant databases containing data on early embryo development and provided an overview. Using dbEmbryo, we obtained a phase-separated model of transcriptional control during early embryo development. dbEmbryo offers web-based analytical tools and a comprehensive resource for biologists and clinicians to decipher molecular regulatory mechanisms of human and mouse early embryo development.
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Liu, Tiancheng, Lin Yu, Guohui Ding, Zhen Wang, Lei Liu, Hong Li, and Yixue Li. "Gene Coexpression and Evolutionary Conservation Analysis of the Human Preimplantation Embryos." BioMed Research International 2015 (2015): 1–11. http://dx.doi.org/10.1155/2015/316735.
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Evolutionary developmental biology (EVO-DEVO) tries to decode evolutionary constraints on the stages of embryonic development. Two models—the “funnel-like” model and the “hourglass” model—have been proposed by investigators to illustrate the fluctuation of selective pressure on these stages. However, selective indices of stages corresponding to mammalian preimplantation embryonic development (PED) were undetected in previous studies. Based on single cell RNA sequencing of stages during human PED, we used coexpression method to identify gene modules activated in each of these stages. Through measuring the evolutionary indices of gene modules belonging to each stage, we observed change pattern of selective constraints on PED for the first time. The selective pressure decreases from the zygote stage to the 4-cell stage and increases at the 8-cell stage and then decreases again from 8-cell stage to the late blastocyst stages. Previous EVO-DEVO studies concerning the whole embryo development neglected the fluctuation of selective pressure in these earlier stages, and the fluctuation was potentially correlated with events of earlier stages, such as zygote genome activation (ZGA). Such oscillation in an earlier stage would further affect models of the evolutionary constraints on whole embryo development. Therefore, these earlier stages should be measured intensively in future EVO-DEVO studies.