Similar Datasets
Project description:We report that TET1 mediated 5hmC deposition is necessary for Sox9 function in embryonic cartilage development
2020-11-05 | GSE105121 | GEO
Project description:TET1 KO affects Sox9 function [methylation]
| PRJNA414099 | ENA
Project description:TET1 KO affects Sox9 function [growth plate tissue]
| PRJNA414772 | ENA
Project description:Ten eleven translocation 1 (Tet1) directs chondrogenic differentiation in the mouse embryonic growth plate. We have characterized the global exon array analysis upon Tet1 knockdown induced by two different shRNAs. In this dataset, we include the expression data obtained from in vitro differentiation of ATDC5 chondroprogenitor cells for 15 days in presence (non-target) and absence (Tet1 sh1 and Tet1 sh2) of Tet1. These data are used to obtain the genes which are differentially expressed in absence of Tet1 and to identify the altered signaling pathways.
2020-11-05 | GSE61855 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2020-11-05 | GSE105122 | 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: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: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:The TET proteins TET1, TET2 and TET3 constitute a new family of dioxygenases that utilize molecular oxygen and the cofactors Fe(II) and 2-oxoglutarate to convert 5-methylcytosine (5mC) to 5-hydroxy-methylcytosine (5hmC) and further oxidation products in DNA1-5. Here we show that Tet1 and Tet2 have distinct roles in regulating 5hmC deposition and gene expression in mouse embryonic stem cells (mESC). Tet1 depletion in mESC primarily diminishes 5hmC levels at transcription start sites (TSS), whereas Tet2 depletion is mostly associated with decreased 5hmC in gene bodies relative to TSS. 5hmC is enriched at exon start and end sites, especially in exons that are highly expressed, and is significantly decreased upon Tet2 knockdown at the boundaries of high-expressed exons that are selectively regulated by Tet2. In differentiating murine B cells, Tet2 deficiency is associated with selective exon exclusion in the gene encoding the transmembrane phosphatase CD45. Tet2 depletion is associated with increased 5hmC and decreased 5mC at promoters/ TSS regions, possibly because of the redundant activity of Tet1. Together, these data indicate a complex interplay between Tet1 and Tet2 in mESC, and show that loss-of-function of a single TET protein does not necessarily lead to loss of 5hmC and a corresponding gain of 5mC, as generally assumed. The relation between Tet2 loss-of-function and selective changes in exon expression could potentially explain the frequent occurrence of both TET2 loss-of-function mutations and mutations in proteins involved in pre-mRNA splicing in myeloid malignancies in humans. Gene and exon expression analysis in mESC, Tet1 knockdown mESC, and Tet2 knockdown mESC by RNA-sequencing. Mapping of 5-hydroxymethylcytosine in mESC, Tet1 knockdown mESC, and Tet2 knockdown mESC by anti-CMS-seq. Mapping of methylcytosine in mESC, and Tet2 kd mESC by MeDIP-seq.
2014-01-16 | E-GEOD-50200 | biostudies-arrayexpress