Role of TET1-mediated epigenetic modulation in Alzheimer’s disease [RNA-Seq]
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ABSTRACT:
PROVIDER: PRJNA938432 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Role of TET1-mediated epigenetic modulation in Alzheimer’s disease [5hmC-Capture]
| PRJNA938409 | ENA
Project description:Role of TET1-mediated epigenetic modulation in Alzheimer's disease
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Project description:To investigate the influence the partial loss of Tet1 has on AD pathogenesis in 5xFAD mice, we crossed a Tet1 KO mouse line with the 5xFAD mouse line to generate WT, 5xFAD, Tet1(+/-), and FAD/Tet1(+/-) mice.
2023-10-03 | GSE226043 | GEO
Project description:To investigate the influence the partial loss of Tet1 has on AD pathogenesis in 5xFAD mice, we crossed a Tet1 KO mouse line with the 5xFAD mouse line to generate WT, 5xFAD, Tet1(+/-), and FAD/Tet1(+/-) mice. We then performed gene expression profiling analysis using data obtained from RNA-seq from biological replicates of mice comprised of 4 different genotypes.
2023-10-03 | GSE226053 | GEO
Project description:No disease-modifying drugs exist to treat osteoarthritis (OA), a degenerative disease of the joint. The complexity of OA necessitates a combinational and broad therapeutic approach. Epigenetic regulators are able to control large programs of genes, and recent work from our group and others have showcased systemic epigenetic dysregulation in OA. Previously, we demonstrated that OA chondrocytes accumulate 5-fold more 5-hydroxymethylcytosine (5hmC), an oxidized derivative of methylcytosine (5mC) associated with gene activation, at disease relevant sites. To test if 5hmC has a role in the early onset of OA, we utilized a mouse model of surgically induced OA, destabilization of the medial meniscus (DMM), and found that DMM mice gained ~40,000 differentially hydroxymethylated sites. Genetic loss of TET1, the enzyme responsible for 5hmC deposition, prevented pathologic gain of 5hmC, activation of many OA pathways, and protected mice from OA development. To test the clinical potential of a TET1 based OA therapy, we injected 2-hydroxyglutarate (2-HG), a TET inhibitor, into the joint after DMM induction and observed stalled disease progression. Collectively, these data show that TET1 mediated 5hmC deposition regulates multiple OA pathways and that its modulation can be a powerful clinical tool for OA.
2020-07-13 | GSE143447 | GEO
Project description:Precise regulation of DNA methylation in mammals is critical for genome stability and epigenetic regulation. The discovery of the ten-eleven translocation (TET) proteins catalyzing the oxidation from 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC) revolutionized the perspective on the complexity and regulation of DNA modifications. Despite accumulating knowledge about the role of TET1, it remains unclear to what extent these can be attributed to its catalytic activity. Here, we use genome engineering and quantitative multi-omics approaches to dissect the role and mechanism of TET1 in mESCs. Our study identifies TET1 as an essential interaction hub for multiple chromatin modifying complexes and as a global regulator of histone modifications. Strikingly, we find that the majority of transcriptional regulation depends on non-catalytic functions of TET1. Moreover, we show that the establishment of H3K9me3 and H4K20me3 at ERV1, ERVK, and ERVL is mediated by TET1 independent of DNA demethylation. We provide evidence that repression of endogenous retroviruses depends on the interaction between TET1 and SIN3A. In summary, we demonstrate that the non-catalytic functions of TET1 are critical for regulation of gene expression and the silencing of endogenous retroviruses in mESCs.
2022-08-31 | PXD028850 | Pride
Project description:DNA hydroxymethylation by epigenetic modifiers TET dioxygenases is critical for gene transcription in various biological processes, however, its role in oligodendrocyte maturation and functions remain elusive. Here, we found that mice lacking Tet1 in the oligodendrocyte lineage exhibited hypomyelination in the CNS in the juvenile stage, leading to defects in action potential propagation, motor coordination, anxiety-like behavior and spatial memory capacities. Although the myelin deficiency recovered in adulthood, remyelination after cuprizone-induced demyelination was compromised in Tet1cKO mice. By integrating transcriptome and DNA methylation profiles, we identified a cohort of genes that were differentially regulated by Tet1 and hyperhydroxymethylation, including the genes associated with Ca2+ transportation. Tet1-deficient OPCs exhibited a reduction in [Ca2+] oscillations, while the agonists of calcium internal stores rescued the differentiation defect of Tet1-deficient OPCs. Thus, our results suggest that stage-specific Tet1-mediated epigenetic programming in oligodendrocytes maintain Ca2+ homeostasis for differentiation and regulate neuronal activities and myelin repair.
2019-11-20 | GSE122838 | GEO
Project description:No disease-modifying drugs exist to treat osteoarthritis (OA), a degenerative disease of the joint. The complexity of OA necessitates a combinational and broad therapeutic approach. Epigenetic regulators are able to control large programs of genes, and recent work from our group and others have showcased systemic epigenetic dysregulation in OA. Previously, we demonstrated that OA chondrocytes accumulate 5-fold more 5-hydroxymethylcytosine (5hmC), an oxidized derivative of methylcytosine (5mC) associated with gene activation, at disease relevant sites. To test if 5hmC has a role in the early onset of OA, we utilized a mouse model of surgically induced OA, destabilization of the medial meniscus (DMM), and found that DMM mice gained ~40,000 differentially hydroxymethylated sites. Genetic loss of TET1, the enzyme responsible for 5hmC deposition, prevented pathologic gain of 5hmC, activation of many OA pathways, and protected mice from OA development. To test the clinical potential of a TET1 based OA therapy, we injected 2-hydroxyglutarate (2-HG), a TET inhibitor, into the joint after DMM induction and observed stalled disease progression. Collectively, these data show that TET1 mediated 5hmC deposition regulates multiple OA pathways and that its modulation can be a powerful clinical tool for OA.
2020-07-13 | GSE143575 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2023-10-03 | GSE226056 | GEO
Project description:Epigenetic remodeling is essential for oncogene-induced cellular transformation and malignancy. In contrast to histone posttranslational modification, how oncogenic signaling remodels DNA methylation remains poorly understood. The oncoprotein YAP, a coactivator of the TEAD transcription factors mediating Hippo signaling, is widely activated in human cancer. Here we identify the 5-methylcytosine dioxygenase TET1 as a direct YAP target and a master regulator that coordinates the genome-wide epigenetic and transcriptional reprogramming of YAP target genes in the liver. YAP activation induces the expression of TET1, which physically interacts with TEAD to cause regional DNA demethylation, histone H3K27 acetylation and chromatin opening in YAP target genes to facilitate transcriptional activation. Loss of TET1 not only reverses YAP-induced epigenetic and transcriptional changes but also suppresses YAP-induced hepatomegaly and tumorigenesis. These findings exemplify how oncogenic signaling regulates site specificity of DNA demethylation to promote tumorigenesis and implicate TET1 as a potential target for modulating YAP signaling in physiology and diseases.
2022-05-09 | GSE178227 | GEO