Flame retardant tetrabromobisphenol A (TBBPA) disrupts histone acetylation and zygotic transcription during zebrafish embryogenesis
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PROVIDER: PRJNA1093380 | ENA |
REPOSITORIES: ENA
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Project description:3,3’,5.5’-Tetrabromobisphenol A (TBBPA) is a widely used brominated flame-retardant utilized in the production of electronic devices and plastic paints. The objective of this study is to use zebrafish as a model and determine the effects of TBBPA exposure on early embryogenesis. We initiated TBBPA exposures (0, 10, 20 and 40μM) at 0.75 h post fertilization (hpf) and monitored early developmental events such as cleavage, blastula and epiboly that encompass maternal-to-zygotic transition (MZT) and zygotic genome activation (ZGA). Our data revealed that TBBPA exposures induced onset of developmental delays by 3 hpf (blastula). By 5.5 hpf (epiboly), TBBPA-exposed (10-20 μM) embryos showed concentration-dependent developmental lag by up to 3 stages or 100% mortality at 40 μM. Interestingly, while continued 0.75- 48 hpf TBBPA exposures (10 μM) led to severely deformed embryos, replacing exposure solution with chemical-free media at 6 hpf mitigated this effect, with 100% normal embryos at 48 hpf. To examine the genetic basis of TBBPA-induced delays, we conducted mRNA-sequencing on embryos exposed to 0 or 40 μM TBBPA from 0.75 hpf to 2, 3.5 or 4.5 hpf. Read count data showed that while TBBPA exposures had no overall impacts on maternal or maternal-zygotic genes, collective read counts for zygotically activated genes were lower in TBBPA treatment at 4.5 hpf compared to time-matched controls, suggesting that TBBPA delays ZGA. Gene ontology assessments for both time- and stage-matched differentially expressed genes revealed TBBPA-induced inhibition of chromatin assembly- a process regulated by histone modifications. Since acetylation is the primary histone modification system operant during early ZGA, we hypothesized that TBBPA inhibits histone acetylation, resulting in lack of open chromatin within promoters of zygotic genes and delaying ZGA. Therefore, we co-exposed embryos to 20 μM TBBPA and 100 μM N-(4-Chloro-3-(trifluoromethyl)phenyl)-2-ethoxybenzamide (CTB) -a histone acetyltransferase activator that promotes histone acetylation- and showed that TBBPA-CTB co-exposures from 0.75- 3 hpf significantly reversed TBBPA-only developmental delays, suggesting that TBBPA-induced phenotypes are indeed driven by repression of histone acetylation. Collectively, our work demonstrates that TBBPA disrupts ZGA and early developmental morphology, potentially by inhibiting histone acetylation. Future studies will focus on mechanisms of TBBPA-induced chromatin modifications.
2024-08-31 | GSE262783 | GEO
Project description:Halogenated flame retardants (HFRs) Tetrabromobisphenol A (TBBPA), Tetrabromobisphenol S (TBBPS) and Tetrachlorobisphenol (TCBPA) are wildly applied in manufacturing industry to improve the fire safety of the products. Recent reports demonstrated that TBBPA, TBBPS and TCBPA can be detected in pregnant women serum at nanomolar-level. Considering TBBPA have also been detected in the cord serum and the structural similarity of the 3 HFRs, it is necessary to pay attention to their development toxicity. Liver is the important detoxic organ but also target of TBBPA since it has been demonstrated that TBBPA exposure lead to increased liver weight in mouse and rat. So the developmental hepatic toxicity of the 3 HFRs were studied in this current research with the transcriptomic and human embryonic stem cells hepatic differentiation based toxicity evaluation system. A hepatic differentiation specific lineage development map and cell lineage - gene expression annotations were made and used for easily assessing the lineage alternations caused by toxicant treatment. Together with GO and KEGG analysis, this study mainly demonstrated that, the 3 HFRs have many common disruptive effect on hepatic differentiation, while only TCBPA significantly inhibited hepatic differentiation. The up-regulation of genes related to cell cycle and FGF10 signaling pathway at relatively late stage of hepatic differentiation indicates the proliferation of hepatoblasts were promoted by the 3 HFRs, likely via up-regulating the FGF10 signaling pathway. The proliferating promoting effect may partly explain why liver gain weight in rodents exposed to TBBPA.
2023-04-03 | GSE148518 | GEO
Project description:Tetrabromobisphenol A (TBBPA) biodegradation in acidogenic systems: one step further on where and who
| PRJEB49191 | ENA
Project description:Early embryogenesis is characterized by the maternal to zygotic transition (MTZ), in which maternally deposited messenger RNAs are translated and subsequently degraded while zygotic transcription begins. Posttranscriptional gene regulation by RNA-binding proteins (RBPs) is a dominant force controlling pre-zygotic gene expression. Here we describe the first in vivo mRNA-bound proteome in early Drosophila melanogaster embryos. mRNA interactome capture using conventional (254nm) and photoactivatable ribonucleoside-enhanced UV-crosslinking (365nm) was applied to detect RBPs bound to maternal and early zygotic polydenylated transcripts within the first two hours of embryogenesis. We identified a high confidence set of 476 putative RBPs and confirmed RNA-binding activity for most of the tested candidates. The majority of the identified proteins in the early fly mRNA interactome were known RBPs, harboring canonical RBPs features. Nearly hundred of the identified proteins were previously not known to bind RNA. Interestingly, mRNAs encoding RBPs and TFs exhibit time specific expression modules, in which RBPs dominate the first hours of embryonic development. Using fly-FISH data, we could show enriched RBP localization in the posterior embryo during these first hours of fly embryogenesis, suggesting general importance germ cell maturation.
2016-04-26 | PXD002992 | Pride
Project description:To identify liver transcripts differentially expressed due to treatment with tetrabromobisphenol A-bis(2,3-dibromopropyl ether) (TBBPA-DBPE), we collected RNA from male Harlan Sprague Dawley rats exposed to 0, 0.1, 0.94, 9.4, 94.3 or 943 mg/kg TBBPA.DBPE, 5 days after exposure for animals 7 weeks of age. These samples were interrogated with the Affymetrix Rat Genome 230 2.0 GeneChip array. A total of 0,0,0,0,0, and 0 gene transcripts were differentially expressed due to TBBPA.DBPE treatment after exposure to 0.1, 0.94, 9.4, 94.3 or 943 mg/kg TBBPA.DBPE (false discovery rate (FDR) < 0.05).
2020-07-15 | GSE153363 | GEO
Project description:Background: Early embryonic developmental programs are guided by the coordinated interplay between maternally inherited and zygotically manufactured RNAs and proteins. Although these processes happen concomitantly and affecting gene function during this period is bound to affect both pools of mRNAs, it has been challenging to study their expression dynamics separately. Results: By employing Slam-seq, a nascent mRNA labeling transcriptomic approach, in a developmental time series we observe that over half of the early zebrafish embryo transcriptome consists of maternal-zygotic genes, emphasizing their pivotal role in early embryogenesis. We provide an hourly resolution of de novo transcriptional waves and follow nascent mRNA trajectories, finding that most de novo transcriptional events are stable throughout this period. Additionally, by blocking microRNA430 function, a key post-transcriptional regulator during zebrafish embryogenesis, we directly show that it destabilizes hundreds of de novo transcribed mRNAs from pure zygotic as well as maternal-zygotic genes. This unveils a novel miR-430 function during embryogenesis, fine-tuning zygotic gene expression, which highlights that Slam-seq can be used to disentangle transcriptional and post-transcriptional regulation of mRNA levels. Conclusion: Such valuable insights into zebrafish early embryo transcriptome dynamics emphasize the significance of post-transcriptional regulators in zygotic genome activation. These findings pave the way for future investigations into the coordinated interplay between transcriptional and post-transcriptional landscapes required for the establishment of animal cell identities and functions.
2024-02-10 | GSE247934 | GEO
Project description:Background: Early embryonic developmental programs are guided by the coordinated interplay between maternally inherited and zygotically manufactured RNAs and proteins. Although these processes happen concomitantly and affecting gene function during this period is bound to affect both pools of mRNAs, it has been challenging to study their expression dynamics separately. Results: By employing Slam-seq, a nascent mRNA labeling transcriptomic approach, in a developmental time series we observe that over half of the early zebrafish embryo transcriptome consists of maternal-zygotic genes, emphasizing their pivotal role in early embryogenesis. We provide an hourly resolution of de novo transcriptional waves and follow nascent mRNA trajectories, finding that most de novo transcriptional events are stable throughout this period. Additionally, by blocking microRNA430 function, a key post-transcriptional regulator during zebrafish embryogenesis, we directly show that it destabilizes hundreds of de novo transcribed mRNAs from pure zygotic as well as maternal-zygotic genes. This unveils a novel miR-430 function during embryogenesis, fine-tuning zygotic gene expression, which highlights that Slam-seq can be used to disentangle transcriptional and post-transcriptional regulation of mRNA levels. Conclusion: Such valuable insights into zebrafish early embryo transcriptome dynamics emphasize the significance of post-transcriptional regulators in zygotic genome activation. These findings pave the way for future investigations into the coordinated interplay between transcriptional and post-transcriptional landscapes required for the establishment of animal cell identities and functions.
2024-02-10 | GSE247933 | GEO
Project description:Background: Early embryonic developmental programs are guided by the coordinated interplay between maternally inherited and zygotically manufactured RNAs and proteins. Although these processes happen concomitantly and affecting gene function during this period is bound to affect both pools of mRNAs, it has been challenging to study their expression dynamics separately. Results: By employing Slam-seq, a nascent mRNA labeling transcriptomic approach, in a developmental time series we observe that over half of the early zebrafish embryo transcriptome consists of maternal-zygotic genes, emphasizing their pivotal role in early embryogenesis. We provide an hourly resolution of de novo transcriptional waves and follow nascent mRNA trajectories, finding that most de novo transcriptional events are stable throughout this period. Additionally, by blocking microRNA430 function, a key post-transcriptional regulator during zebrafish embryogenesis, we directly show that it destabilizes hundreds of de novo transcribed mRNAs from pure zygotic as well as maternal-zygotic genes. This unveils a novel miR-430 function during embryogenesis, fine-tuning zygotic gene expression, which highlights that Slam-seq can be used to disentangle transcriptional and post-transcriptional regulation of mRNA levels. Conclusion: Such valuable insights into zebrafish early embryo transcriptome dynamics emphasize the significance of post-transcriptional regulators in zygotic genome activation. These findings pave the way for future investigations into the coordinated interplay between transcriptional and post-transcriptional landscapes required for the establishment of animal cell identities and functions.
2024-02-10 | GSE247930 | GEO
Project description:The significant morphological differences observed during embryo development in angiosperms and gymnosperms are expected to be the result of a differential control of gene expression. We used a loblolly pine (Pinus taeda) cDNA microarray to analyze global transcriptional changes along zygotic embryogenesis in maritime pine (Pinus pinaster). A time-course analysis of the data obtained from the five embryo developmental groups used in this study led to the identification of 4,645 genes whose expression varied along P. pinaster embryogenesis. These transcripts were clustered into six distinct expression profiles. The grouping of these profiles in early, mid-embryogenesis and embryo maturation, according to the developmental period where most of the sequences were up-regulated, evidenced that characteristic transcriptional changes are associated to each developmental period. The application of a cut-off value of 1.95-fold change led to the identification of 1,838 differentially expressed transcripts that were categorized by biological process. Metabolism, interaction with the environment, oxidation-reduction and transport were some of the most represented categories. During early embryogenesis genes putatively involved in phytohormone-mediated signaling were identified, whereas in middle stages the overrepresented genes could be associated with cotyledon formation and induction of somatic embryogenesis. Genes associated with the synthesis of storage products were up-regulated in the latest stages of pine embryo development. It was also during this developmental period that the largest number of sequences putatively encoding transcription factors was identified. Pine immature zygotic embryos were pooled into five different developmental groups according to the collection date (Day0; Day5; Day11; Day15 and Day25). A common reference design was used. Total RNA was extracted from each sample. Three extractions were prepared per sample (biological replicates). A defined ammount from each RNA sample was pooled to use as reference. Messenger RNA was amplified for both test samples and reference. These were hybridized together in two separate experiments (technical replicates). In total, 30 slides were analyzed.
2012-01-30 | E-GEOD-32551 | biostudies-arrayexpress
Project description:Tetrabromobisphenol A (TBBPA) and its substitutes and derivatives have been widely used as halogenated flame retardants (HFRs), in the past few decades. As a consequence, these compounds are frequently detected in the environment, as well as human bodily fluids, especially umbilical cord blood and breast milk. This has raised awareness of their potential risks to fetuses and infants. In this study, we employed human embryonic stem cell differentiation models to assess the potential developmental toxicity of six TBBPA-like compounds, at human relevant nanomolar concentrations. To mimic early embryonic development, we utilized embryoid body-based 3D differentiation in presence of the six HFRs. Transcriptomics data showed that HFR exposure over 16 days of differentiation only interfered with the expression of a few genes, indicating those six HFRs may not have specific tissue/organ targets during embryonic development. Nevertheless, further analyses revealed that some cardiac-related genes were dysregulated. Since the heart is also the first organ to develop, we employed a cardiac differentiation model to analyze the six HFRs' potential developmental toxicity in more depth. Overall, HFRs of interest did not significantly disturb the canonical WNT pathway, which is an essential signal transduction pathway for cardiac development. In addition, the six HFRs showed only mild changes in gene expression levels for cardiomyocyte markers, such as NKX2.5, MYH7, and MYL4, as well as a significant down-regulation of some but not all the epicardial and smooth muscle cell markers selected. Taken together, our results show that the six studied HFRs, at human relevant concentrations, may impose negligible effects on embryogenesis and heart development. Nevertheless, higher exposure doses might affect the early stages of heart development.
2023-02-02 | GSE193176 | GEO