Similar Datasets
Project description:DNA methylation is a critical epigenetic modification in plants that regulates gene expression, silences transposable elements (TEs), and supports proper development. Traditionally, heritable epimutations in plants have been generated using genetic mutants or chemical inhibitors, but these approaches often lack precision or stability. In this study, we investigated the effects of globally altering DNA methylation in tomato, a species with a large, TE-rich genome, through the ectopic expression of the catalytic domain of the human DNA demethylase TEN-ELEVEN TRANSLOCATION3 (hTET3cd). We found that TET3-mediated demethylation induced stable hypomethylation at CG and CHG sites and that these changes were inherited across multiple generations, including in non-transgenic siblings. Interestingly, demethylation in heterochromatic pericentromeric regions was often accompanied by gains in CHH methylation, suggesting the compensatory activation of the RNA-directed DNA methylation (RdDM) pathway. Differentially methylated region (DMR) analysis revealed that CG and CHG methylation loss was widespread, while CHH DMRs showed complex patterns of gain and loss, particularly near gene-rich regions and transposable elements enriched for 24-nt small RNAs. Transcriptomic analyses showed distinct gene expression profiles in both TET3 and non-transgenic progeny, with altered expression of TEs and associated genes. These findings demonstrate that enzymatic manipulation of the methylome via hTET3cd can generate stable, heritable epigenetic variation, and highlight the dynamic interplay between targeted DNA demethylation and endogenous mechanisms that act to restore epigenetic homeostasis.
2026-03-13 | GSE303360 | GEO
Project description:DNA methylation is a critical epigenetic modification in plants that regulates gene expression, silences transposable elements (TEs), and supports proper development. Traditionally, heritable epimutations in plants have been generated using genetic mutants or chemical inhibitors, but these approaches often lack precision or stability. In this study, we investigated the effects of globally altering DNA methylation in tomato, a species with a large, TE-rich genome, through the ectopic expression of the catalytic domain of the human DNA demethylase TEN-ELEVEN TRANSLOCATION3 (hTET3cd). We found that TET3-mediated demethylation induced stable hypomethylation at CG and CHG sites and that these changes were inherited across multiple generations, including in non-transgenic siblings. Interestingly, demethylation in heterochromatic pericentromeric regions was often accompanied by gains in CHH methylation, suggesting the compensatory activation of the RNA-directed DNA methylation (RdDM) pathway. Differentially methylated region (DMR) analysis revealed that CG and CHG methylation loss was widespread, while CHH DMRs showed complex patterns of gain and loss, particularly near gene-rich regions and transposable elements enriched for 24-nt small RNAs. Transcriptomic analyses showed distinct gene expression profiles in both TET3 and non-transgenic progeny, with altered expression of TEs and associated genes. These findings demonstrate that enzymatic manipulation of the methylome via hTET3cd can generate stable, heritable epigenetic variation, and highlight the dynamic interplay between targeted DNA demethylation and endogenous mechanisms that act to restore epigenetic homeostasis.
2026-03-13 | GSE303400 | GEO
Project description:TET3-mediated DNA demethylation contributes to the formation of stable epialleles in tomato
| PRJNA1295453 | ENA
Project description:TET3-mediated DNA demethylation contributes to the formation of stable epialleles in tomato [RNA-seq]
| PRJNA1294904 | ENA
Project description:TET3-mediated DNA demethylation contributes to the formation of stable epialleles in tomato [low coverage WGBS]
| PRJNA1295346 | ENA
Project description:Expression of the mammalian DNA demethylase enzyme TET3 in plants can be used to induce hypomethylation of DNA. In tomato lines that express a TET3 transgene, we observed distinct phenotypes including an increase in the length and number of leaves of primary shoots. As these changes resemble phenotypes observed in plants with strong expression of SELF PRUNING (SP), a member of the PEBP/CETS family, we investigated in TET3 lines the expression levels of members of the PEBP/CETS gene family, which affect shoot architecture and growth of sympodial units in tomato. We did not detect any changes in SP expression in TET3 lines, but for CEN1.1, a putative family member that has not been functionally characterized, we identified changes in gene expression that corresponded to hypomethylation in the upstream region. In tomato wild type, CEN1.1 is expressed in roots, petals, and shoot apices but not in mature leaves. In contrast, in TET3 transformants, the CEN1.1 gene became hypomethylated and activated in leaves. Ectopic expression of CEN1.1 in tomato caused similar phenotypes to those seen in TET3 transformants. Vegetative growth was increased, resulting both in a delay in inflorescence development and in an instability of the inflorescences, which frequently reverted to a vegetative state. Ectopic expression of CEN1.1 in Arabidopsis thaliana also caused floral repression. Our data suggest that the phenotypes observed in TET3 lines are a consequence of ectopic activation of CEN1.1, which promotes vegetative growth, and that CEN1.1 expression is sensitive to DNA methylation changes.
| S-EPMC6508569 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2017-08-18 | GSE97247 | GEO
Project description:Germline pathogenic variants in chromatin-modifying enzymes are a common cause of pediatric developmental disorders. These enzymes catalyze reactions that regulate epigenetic inheritance via histone post-translational modifications and DNA methylation. Cytosine methylation (5-methylcytosine [5mC]) of DNA is the quintessential epigenetic mark, yet no human Mendelian disorder of DNA demethylation has yet been delineated. Here, we describe in detail a Mendelian disorder caused by the disruption of DNA demethylation. TET3 is a methylcytosine dioxygenase that initiates DNA demethylation during early zygote formation, embryogenesis, and neuronal differentiation and is intolerant to haploinsufficiency in mice and humans. We identify and characterize 11 cases of human TET3 deficiency in eight families with the common phenotypic features of intellectual disability and/or global developmental delay; hypotonia; autistic traits; movement disorders; growth abnormalities; and facial dysmorphism. Mono-allelic frameshift and nonsense variants in TET3 occur throughout the coding region. Mono-allelic and bi-allelic missense variants localize to conserved residues; all but one such variant occur within the catalytic domain, and most display hypomorphic function in an assay of catalytic activity. TET3 deficiency and other Mendelian disorders of the epigenetic machinery show substantial phenotypic overlap, including features of intellectual disability and abnormal growth, underscoring shared disease mechanisms.
| S-EPMC7010978 | biostudies-literature
Project description:Transposable elements (TEs) comprise approximately half of eukaryotic genomes and significantly contribute to genome plasticity. In this study, we focused on a specific TE, MERVL, which exhibits particular expression during the 2-cell stage and commonly serves as an indicator of embryonic totipotency. However, its precise role in embryo development remains mysterious. We utilized DRUG-seq to investigate the effects of oxidative damage on genes and TEs expression. Our findings revealed that exposure to hydrogen peroxide (H2O2) could induce DNA damage, apoptosis, and incomplete DNA demethylation in embryos, which were potentially associated with MERVL expression. To further explore its function, antisense nucleotides (ASO) targeting MERVL were constructed to knockdown the expression in early embryos. Notably, this knockdown led to the occurrence of DNA damage and apoptosis as early as the 2-cell stage, consequently reducing the number of embryos that could progress to the blastocyst stage. Moreover, we discovered that MERVL exerted an influence on the reprogramming of embryonic DNA methylation. In MERVL-deficient embryos, the activity of the DNA demethylase ten-eleven translocation 3 (TET3) was suppressed, resulting in impaired demethylation when compared to normal development. This impairment might underpin the mechanism that impacts embryonic development. Collectively, our study not only verified the crucial role of MERVL in embryonic development but also probed its regulatory function in DNA methylation reprogramming, thereby laying a solid foundation for further investigations into MERVL's role.
| S-EPMC11905524 | biostudies-literature
Project description:An efficient, accurate, and timely DNA damage response (DDR) is crucial for the maintenance of genome integrity. Here, we report that ten-eleven translocation dioxygenase (TET) 3-mediated conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) in response to ATR-dependent DDR regulates DNA repair. ATR-dependent DDR leads to dynamic changes in 5hmC levels and TET3 enzymatic activity. We show that TET3 is an ATR kinase target that oxidizes DNA during ATR-dependent DNA damage repair. Modulation of TET3 expression and activity affects DNA damage signaling and DNA repair and consequently cell death. Our results provide novel insight into ATR-mediated DDR, in which TET3-mediated DNA demethylation is crucial for efficient DNA repair and maintenance of genome stability.
| S-EPMC5412826 | biostudies-literature