DNA methylation changes during preimplantation development reveal inter species-differences and reprogramming events at imprinted genes
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ABSTRACT:
ORGANISM(S): Sus scrofa Bos taurus
PROVIDER: GSE143850 | GEO | 2020/05/20
REPOSITORIES: GEO
Similar Datasets
Project description:Preimplantation embryos experience profound resetting of epigenetic information inherited from the gametes. Genome-wide analysis at single-base resolution has shown similarities but also species differences between human and mouse preimplantation embryos in DNA methylation patterns and reprogramming. Here, we have extended such analysis to two key livestock species, the pig and the cow. We generated genome-wide DNA methylation and whole-transcriptome datasets from gametes to blastocysts in both species. In oocytes from both species, a distinctive bimodal methylation landscape is present, with hypermethylated domains prevalent over hypomethylated domains, similar to human, while in the mouse the proportions are reversed.An oocyte-like pattern of methylation persists in the cleavage stages, albeit with some reduction in methylation level, persisting to blastocysts in cow, while pig blastocysts have a highly hypomethylated landscape. In the pig, there was evidence of transient de novo methylation at the 8-16 cell stages of domains unmethylated in oocytes, revealing a complex dynamic of methylation reprogramming. The methylation datasets were used to identify germline differentially methylated regions (gDMRs) of known imprinted genes and for the basis of detection of novel imprinted loci. Strikingly in the pig, we detected a consistent reduction in gDMR methylation at the 8-16 cell stages, followed by recovery to the blastocyst stage, suggesting an active period of imprint stabilization in preimplantation embryos. Transcriptome analysis revealed absence of expression in oocytes of both species of ZFP57, a key factor in the mouse for gDMR methylation maintenance, but presence of the alternative imprint regulator ZNF445. In conclusion, our study reveals species differences in DNA methylation reprogramming and suggests that porcine or bovine models may be closer to human in key aspects than in the mouse model.
| S-EPMC7216732 | biostudies-literature
Project description:Preimplantation embryos experience profound resetting of epigenetic information. Genome-wide analysis at single-base resolution had shown relevant species differences between human and mouse preimplantation embryos. Thus, we have extended such analysis to two key livestock species, the pig and the cow. We generated data showing the genome-wide DNA methylation landscape and whole-transcriptomes from gametes to blastocysts in both species. Detailed analysis revealed species specific differences and new insights in biological paradigms. An oocyte-like pattern of methylation in the cleavage stages, albeit with some reduction in methylation level, appears to persist even in cow blastocysts. Hypermethylated domains were prevalent over hypomethylated domains in pigs and cows, similar to human, while in the mouse the pattern is reversed. Interestingly, the behaviour of the oocyte hypo-domains in cleavage embryos revealed a complex dynamic of methylation reprogramming. It shows a pronounced increase in methylation at the 8-16 cell stage in pigs, similar to human, concomitant with ZFP57 expression. Even it is widely accepted that imprinted genes are established in the parental germline and robustly maintained through early development, our data show a greater dynamic of methylation in germline differentially methylated regions and few appear to maintain the expected 50% methylation from the 2-4 cell stage to blastocyst stage. It reveals that an active period of imprint stabilization until the blastocyst stage is required
2020-05-20 | GSE143849 | GEO
Project description:Preimplantation embryos experience profound resetting of epigenetic information. Genome-wide analysis at single-base resolution had shown relevant species differences between human and mouse preimplantation embryos. Thus, we have extended such analysis to two key livestock species, the pig and the cow. We generated data showing the genome-wide DNA methylation landscape and whole-transcriptomes from gametes to blastocysts in both species. Detailed analysis revealed species specific differences and new insights in biological paradigms. An oocyte-like pattern of methylation in the cleavage stages, albeit with some reduction in methylation level, appears to persist even in cow blastocysts. Hypermethylated domains were prevalent over hypomethylated domains in pigs and cows, similar to human, while in the mouse the pattern is reversed. Interestingly, the behaviour of the oocyte hypo-domains in cleavage embryos revealed a complex dynamic of methylation reprogramming. It shows a pronounced increase in methylation at the 8-16 cell stage in pigs, similar to human, concomitant with ZFP57 expression. Even it is widely accepted that imprinted genes are established in the parental germline and robustly maintained through early development, our data show a greater dynamic of methylation in germline differentially methylated regions and few appear to maintain the expected 50% methylation from the 2-4 cell stage to blastocyst stage. It reveals that an active period of imprint stabilization until the blastocyst stage is required
2020-05-20 | GSE143848 | GEO
Project description:An amendment to this paper has been published and can be accessed via the original article.
| S-EPMC7322833 | biostudies-literature
Project description:DNA methylation changes during preimplantation development reveal inter species-differences and reprogramming events at imprinted genes
| PRJNA601892 | ENA
Project description:DNA methylation changes during preimplantation development reveal inter species-differences and reprogramming events at imprinted genes [BS-Seq]
| PRJNA601899 | ENA
Project description:DNA methylation changes during preimplantation development reveal inter species-differences and reprogramming events at imprinted genes [RNA-Seq]
| PRJNA601900 | ENA
Project description:Human preimplantation development is characterized by low developmental rates that are poorly understood. Early mammalian embryogenesis is characterized by a major phase of epigenetic reprogramming, which involves global DNA methylation changes and activity of TET enzymes; the importance of DNA methylation reprogramming for successful human preimplantation development has not been investigated. Here, we analyzed early human embryos for dynamic changes in 5-methylcytosine and its oxidized derivatives generated by TET enzymes. We observed that 5-methylcytosine and 5-hydroxymethylcytosine show similar, albeit less pronounced, asymmetry between the parental pronuclei of human zygotes relative to mouse zygotes. Notably, we detected low levels of 5-formylcytosine and 5-carboxylcytosine, with no apparent difference in maternal or paternal pronuclei of human zygotes. Analysis of later human preimplantation stages revealed a mosaic pattern of DNA 5C modifications similar to those of the mouse and other mammals. Strikingly, using noninvasive time-lapse imaging and well-defined cell cycle parameters, we analyzed normally and abnormally developing human four-cell embryos for global reprogramming of DNA methylation and detected lower 5-methylcytosine and 5-hydroxymethylcytosine levels in normal embryos compared to abnormal embryos. In conclusion, our results suggest that DNA methylation reprogramming is conserved in humans, with human-specific dynamics and extent. Furthermore, abnormalities in the four-cell-specific DNA methylome in early human embryogenesis are associated with abnormal development, highlighting an essential role of epigenetic reprogramming for successful human embryogenesis. Further research should identify the underlying genomic regions and cause of abnormal DNA methylation reprogramming in early human embryos.
| S-EPMC8460514 | biostudies-literature
Project description:BackgroundThe reproducibility of transcriptomic biomarkers across datasets remains poor, limiting clinical application. We and others have suggested that this is in-part caused by differential error-structure between datasets, and their incomplete removal by pre-processing algorithms.MethodsTo test this hypothesis, we systematically assessed the effects of pre-processing on biomarker classification using 24 different pre-processing methods and 15 distinct signatures of tumour hypoxia in 10 datasets (2,143 patients).ResultsWe confirm strong pre-processing effects for all datasets and signatures, and find that these differ between microarray versions. Importantly, exploiting different pre-processing techniques in an ensemble technique improved classification for a majority of signatures.ConclusionsAssessing biomarkers using an ensemble of pre-processing techniques shows clear value across multiple diseases, datasets and biomarkers. Importantly, ensemble classification improves biomarkers with initially good results but does not result in spuriously improved performance for poor biomarkers. While further research is required, this approach has the potential to become a standard for transcriptomic biomarkers.
| S-EPMC4061774 | biostudies-literature
Project description:Long intergenic noncoding RNAs (lincRNAs) are derived from thousands of loci in mammalian genomes and are frequently enriched in transposable elements (TEs). Although families of TE-derived lincRNAs have recently been implicated in the regulation of pluripotency, little is known of the specific functions of individual family members. Here we characterize three new individual TE-derived human lincRNAs, human pluripotency-associated transcripts 2, 3 and 5 (HPAT2, HPAT3 and HPAT5). Loss-of-function experiments indicate that HPAT2, HPAT3 and HPAT5 function in preimplantation embryo development to modulate the acquisition of pluripotency and the formation of the inner cell mass. CRISPR-mediated disruption of the genes for these lincRNAs in pluripotent stem cells, followed by whole-transcriptome analysis, identifies HPAT5 as a key component of the pluripotency network. Protein binding and reporter-based assays further demonstrate that HPAT5 interacts with the let-7 microRNA family. Our results indicate that unique individual members of large primate-specific lincRNA families modulate gene expression during development and differentiation to reinforce cell fate.
| S-EPMC4827613 | biostudies-literature