Dynamic methylome remodeling throughout mammalian fetal development
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE100685 | GEO | 2018/06/30
REPOSITORIES: GEO
Similar Datasets
Project description:Assisted Reproductive Technologies (ART) employ gamete/embryo handling and culture in vitro to produce offspring. ART pregnancies have increased risk of low birth weight, abnormal placentation, pregnancy complications, and imprinting disorders. We and others have previously shown that embryo culture induces low birth weight, abnormal placental morphology, and lower levels of DNA methylation in placentas in a mouse model of ART. We hypothesized that these adverse effects are linked to a subtle disruption of specific biological processes during preimplantation development. To test this hypothesis, we performed embryo culture for several discrete periods of preimplantation development and assessed fetal and placental outcomes at term. We observed a reduction in fetal:placental ratio in two distinct windows of preimplantation embryo development, while placental morphological abnormalities and reduced imprinting control region methylation were associated with culture prior to the morula stage. We also provide evidence that extended culture to the blastocyst stage induces additional placental DNA methylation changes compared to embryos transferred at the morula stage, and that female concepti exhibited a higher loss of DNA methylation than males. Altogether, this study identifies specific developmental windows of susceptibility and potential targets for embryo culture optimization.
2022-04-11 | GSE193271 | GEO
Project description:While DNA methylation in other tissues can be approximated through model species, the dynamic distribution and regulatory significance of DNA methylation in the rumen, a unique organ in ruminant, remain largely unknown. Here, we employed whole-genome bisulfite sequencing (WGBS), transcriptomics, and histone modification data to compare fetal and adult stages of bovine rumen with other tissues, including pluripotent stem cells (PSCs) approximating pre-implantation embryos. We found extensive methylation differences, including CG methylation (mCG) and non-CG methylation (mCH; H represents A, C and T) between the rumen at fetal and adult stages and other tissues and PSCs. These differentially methylated regions (DMRs) are closely associated with other epigenetic regulatory components, such as transcription factors (TFs) and histone modifications. These DMRs can also combine to form large hypo CG-DMRs to regulate a cluster of functionally related genes. We elucidated the reasons for morphological and functional differences between fetal and adult rumen at the epigenetic level and the interactions between epigenetic modifications and gene expression. This study highlights the differences in methylation patterns between the rumen and other tissues during development and the role of DNA methylation in controlling gene expression and establishing tissue-specific functions.
2024-06-01 | GSE264345 | GEO
Project description:While DNA methylation in other tissues can be approximated through model species, the dynamic distribution and regulatory significance of DNA methylation in the rumen, a unique organ in ruminant, remain largely unknown. Here, we employed whole-genome bisulfite sequencing (WGBS), transcriptomics, and histone modification data to compare fetal and adult stages of bovine rumen with other tissues, including pluripotent stem cells (PSCs) approximating pre-implantation embryos. We found extensive methylation differences, including CG methylation (mCG) and non-CG methylation (mCH; H represents A, C and T) between the rumen at fetal and adult stages and other tissues and PSCs. These differentially methylated regions (DMRs) are closely associated with other epigenetic regulatory components, such as transcription factors (TFs) and histone modifications. These DMRs can also combine to form large hypo CG-DMRs to regulate a cluster of functionally related genes. We elucidated the reasons for morphological and functional differences between fetal and adult rumen at the epigenetic level and the interactions between epigenetic modifications and gene expression. This study highlights the differences in methylation patterns between the rumen and other tissues during development and the role of DNA methylation in controlling gene expression and establishing tissue-specific functions.
2024-06-01 | GSE264341 | GEO
Project description:While DNA methylation in other tissues can be approximated through model species, the dynamic distribution and regulatory significance of DNA methylation in the rumen, a unique organ in ruminant, remain largely unknown. Here, we employed whole-genome bisulfite sequencing (WGBS), transcriptomics, and histone modification data to compare fetal and adult stages of bovine rumen with other tissues, including pluripotent stem cells (PSCs) approximating pre-implantation embryos. We found extensive methylation differences, including CG methylation (mCG) and non-CG methylation (mCH; H represents A, C and T) between the rumen at fetal and adult stages and other tissues and PSCs. These differentially methylated regions (DMRs) are closely associated with other epigenetic regulatory components, such as transcription factors (TFs) and histone modifications. These DMRs can also combine to form large hypo CG-DMRs to regulate a cluster of functionally related genes. We elucidated the reasons for morphological and functional differences between fetal and adult rumen at the epigenetic level and the interactions between epigenetic modifications and gene expression. This study highlights the differences in methylation patterns between the rumen and other tissues during development and the role of DNA methylation in controlling gene expression and establishing tissue-specific functions.
2024-06-01 | GSE264339 | GEO
Project description:While DNA methylation in other tissues can be approximated through model species, the dynamic distribution and regulatory significance of DNA methylation in the rumen, a unique organ in ruminant, remain largely unknown. Here, we employed whole-genome bisulfite sequencing (WGBS), transcriptomics, and histone modification data to compare fetal and adult stages of bovine rumen with other tissues, including pluripotent stem cells (PSCs) approximating pre-implantation embryos. We found extensive methylation differences, including CG methylation (mCG) and non-CG methylation (mCH; H represents A, C and T) between the rumen at fetal and adult stages and other tissues and PSCs. These differentially methylated regions (DMRs) are closely associated with other epigenetic regulatory components, such as transcription factors (TFs) and histone modifications. These DMRs can also combine to form large hypo CG-DMRs to regulate a cluster of functionally related genes. We elucidated the reasons for morphological and functional differences between fetal and adult rumen at the epigenetic level and the interactions between epigenetic modifications and gene expression. This study highlights the differences in methylation patterns between the rumen and other tissues during development and the role of DNA methylation in controlling gene expression and establishing tissue-specific functions.
2024-06-01 | GSE264336 | GEO
Project description:While DNA methylation in other tissues can be approximated through model species, the dynamic distribution and regulatory significance of DNA methylation in the rumen, a unique organ in ruminant, remain largely unknown. Here, we employed whole-genome bisulfite sequencing (WGBS), transcriptomics, and histone modification data to compare fetal and adult stages of bovine rumen with other tissues, including pluripotent stem cells (PSCs) approximating pre-implantation embryos. We found extensive methylation differences, including CG methylation (mCG) and non-CG methylation (mCH; H represents A, C and T) between the rumen at fetal and adult stages and other tissues and PSCs. These differentially methylated regions (DMRs) are closely associated with other epigenetic regulatory components, such as transcription factors (TFs) and histone modifications. These DMRs can also combine to form large hypo CG-DMRs to regulate a cluster of functionally related genes. We elucidated the reasons for morphological and functional differences between fetal and adult rumen at the epigenetic level and the interactions between epigenetic modifications and gene expression. This study highlights the differences in methylation patterns between the rumen and other tissues during development and the role of DNA methylation in controlling gene expression and establishing tissue-specific functions.
2024-06-01 | GSE264333 | GEO
Project description:Background: Plant-unique RNA polymerase IV (Pol IV) governs the establishment of small RNA-directed DNA methylation (RdDM) and contributes to the maintenance of transposable element (TE) silencing. Pol IV-dependent RdDM is highly active during embryonic development, and its absence occasionally reduces seed sets in species with high TE content. However, the mechanism underlying embryonic development failure due to the loss of Pol IV-RdDM remains largely unclear. Results: Here, we report that the loss-of-function of SlNRPD1, encoding the largest subunit of the Pol IV complex leads to aberrant embryogenesis in tomato (Solanum lycopersicum). The slnrpd1 mutants show non-CG hypomethylation and a burst of 21/22-nt sRNA from the distal chromatin region. We found that non-CG hypomethylation at the gene body region is generally associated with the activation of transcription, and knocking out DEMETER-like DNA demethylases cannot reverse slnrpd1 embryo lethality. mCHH hypomethylation in slnrpd1 disrupts gene expression related to auxin and WUSCHEL-related homeobox (WOX) signaling. TE reactivation in slnrpd1 mainly affects the expression of a limited number of nearby genes rather than contributing to excessive sRNA. Conclusion: We conclude that Pol IV-mediated RdDM is essential for tomato embryogenesis via non-CG methylation. mCHH hypomethylation in the slnrpd1 embryo leads to abnormal auxin/WOX signaling and TE reactivation which probably disrupts the tissue and organ initiation. This study provides new insights into the epigenetic regulation of gene and TE expression during embryogenesis. Keywords: DNA methylation, RdDM, NRPD1, Embryogenesis, Tomato
2024-10-01 | GSE246017 | GEO
Project description:Background: Plant-unique RNA polymerase IV (Pol IV) governs the establishment of small RNA-directed DNA methylation (RdDM) and contributes to the maintenance of transposable element (TE) silencing. Pol IV-dependent RdDM is highly active during embryonic development, and its absence occasionally reduces seed sets in species with high TE content. However, the mechanism underlying embryonic development failure due to the loss of Pol IV-RdDM remains largely unclear. Results: Here, we report that the loss-of-function of SlNRPD1, encoding the largest subunit of the Pol IV complex leads to aberrant embryogenesis in tomato (Solanum lycopersicum). The slnrpd1 mutants show non-CG hypomethylation and a burst of 21/22-nt sRNA from the distal chromatin region. We found that non-CG hypomethylation at the gene body region is generally associated with the activation of transcription, and knocking out DEMETER-like DNA demethylases cannot reverse slnrpd1 embryo lethality. mCHH hypomethylation in slnrpd1 disrupts gene expression related to auxin and WUSCHEL-related homeobox (WOX) signaling. TE reactivation in slnrpd1 mainly affects the expression of a limited number of nearby genes rather than contributing to excessive sRNA. Conclusion: We conclude that Pol IV-mediated RdDM is essential for tomato embryogenesis via non-CG methylation. mCHH hypomethylation in the slnrpd1 embryo leads to abnormal auxin/WOX signaling and TE reactivation which probably disrupts the tissue and organ initiation. This study provides new insights into the epigenetic regulation of gene and TE expression during embryogenesis. Keywords: DNA methylation, RdDM, NRPD1, Embryogenesis, Tomato
2024-10-01 | GSE246016 | GEO
Project description:Background: Plant-unique RNA polymerase IV (Pol IV) governs the establishment of small RNA-directed DNA methylation (RdDM) and contributes to the maintenance of transposable element (TE) silencing. Pol IV-dependent RdDM is highly active during embryonic development, and its absence occasionally reduces seed sets in species with high TE content. However, the mechanism underlying embryonic development failure due to the loss of Pol IV-RdDM remains largely unclear. Results: Here, we report that the loss-of-function of SlNRPD1, encoding the largest subunit of the Pol IV complex leads to aberrant embryogenesis in tomato (Solanum lycopersicum). The slnrpd1 mutants show non-CG hypomethylation and a burst of 21/22-nt sRNA from the distal chromatin region. We found that non-CG hypomethylation at the gene body region is generally associated with the activation of transcription, and knocking out DEMETER-like DNA demethylases cannot reverse slnrpd1 embryo lethality. mCHH hypomethylation in slnrpd1 disrupts gene expression related to auxin and WUSCHEL-related homeobox (WOX) signaling. TE reactivation in slnrpd1 mainly affects the expression of a limited number of nearby genes rather than contributing to excessive sRNA. Conclusion: We conclude that Pol IV-mediated RdDM is essential for tomato embryogenesis via non-CG methylation. mCHH hypomethylation in the slnrpd1 embryo leads to abnormal auxin/WOX signaling and TE reactivation which probably disrupts the tissue and organ initiation. This study provides new insights into the epigenetic regulation of gene and TE expression during embryogenesis. Keywords: DNA methylation, RdDM, NRPD1, Embryogenesis, Tomato
2024-10-01 | GSE246015 | GEO
Project description:Organoids derived from human pluripotent stem cells recapitulate the early three-dimensional organization of human brain, but whether they establish the epigenomic and transcriptional programs essential for brain development is unknown. We compared epigenomic and gene regulatory features in cerebral organoids and human fetal brain, using genome-wide, base resolution DNA methylome and transcriptome sequencing. Transcriptomic dynamics in organoids faithfully modeled gene expression trajectories in early-to-mid human fetal brains. We found that early non-CG methylation accumulation at super-enhancers in both fetal brain and organoids marks forthcoming transcriptional repression in the fully developed brain. 74% of 35,627 demethylated regions identified during organoid differentiation overlapped with fetal brain regulatory elements. Interestingly, pericentromeric repeats showed widespread demethylation in multiple types of in vitro human neural differentiation models but not in fetal brain. Our study reveals that organoids recapitulate many epigenomic features of mid-fetal human brain and also identified novel non-CG methylation signatures of brain development.
2016-12-20 | GSE82022 | GEO