Tet1 is a tumor suppressor of hematopoietic maligancy [RNA-Seq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE65955 | GEO | 2015/04/12
SECONDARY ACCESSION(S): PRJNA275549
REPOSITORIES: GEO
Similar Datasets
Project description:Loss of Tet1 expression causes global 5mC and 5hmC changes in stem and progenitor cells in mice and enhanced pro-B cell self-renewal, increased DNA damage and B-lymphomageneis. In this study we performed whole transciptome analysis using RNA-sequencing in purified long-term HSCs and MPPs. These results revealed that genes regulated byTet1 included Histones, DNA repair enzymes and B-lineage specific factors. Purified long-term HSCs and MPPs from WT and Tet1 KO mice were used for RNA isolation. RNA was extracted using RNeasy kit (Qiagen) and PolyA selection using oligo-dT beads (Life Technologies) was performed according to the manufacturer’s instructions. Libraries were generated as described before, including end-repair, A-tailing, adapter (Illumina Truseq system) ligation and PCR amplification. RNA libraries were then sequenced on the Illumina HiSeq 2000 using 50bp paired-end reads. Transcriptome profiling of LT-HSC and MPP cells in WT and Tet1 KO mice
2015-04-12 | E-GEOD-65955 | biostudies-arrayexpress
Project description:Loss of Tet1 expression causes global 5mC and 5hmC changes in stem and progenitor cells in mice and causes enhanced Pro-B cell self-renewal, increased DNA damage and B-lymphomageneis. In this study we performed microarray analysis of total LSK cells from WT and Tet1 KO mice. These results revealed that genes regulated byTet1 in LSKs included Histones, DNA repair enzymes and B-lineage specific factors.
2015-04-12 | GSE65913 | GEO
Project description:Loss of Tet1 expression causes global 5mC and 5hmC changes in stem and progenitor cells in mice and causes enhanced Pro-B cell self-renewal, increased DNA damage and B-lymphomageneis. In this study we performed microarray analysis of total LSK cells from WT and Tet1 KO mice. These results revealed that genes regulated byTet1 in LSKs included Histones, DNA repair enzymes and B-lineage specific factors. LSK cells were purified from the bone marrow of 6-month old WT and Tet1 KO mice . RNA was extracted using RNeasy kit (Qiagen) and hybridized on Affymetrix microarrays. Microarray profiling of LSK cells in WT and Tet1 KO mice.
2015-04-12 | E-GEOD-65913 | biostudies-arrayexpress
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:Loss of Tet1 expression causes global 5mC and 5hmC changes in stem and progenitor cells in mice and causes enhanced Pro-B cell self-renewal, increased DNA damage and B-lymphomageneis. In this study we performed reduced representative bisulfite sequencing (RRBS) of DNA from WT and Tet1 KO LSK cells.
2015-04-12 | GSE65919 | GEO
Project description:Loss of Tet1 expression causes global 5mC and 5hmC changes in stem and progenitor cells in mice and causes enhanced Pro-B cell self-renewal, increased DNA damage and B-lymphomageneis. In this study we performed reduced representative bisulfite sequencing (RRBS) of DNA from WT and Tet1 KO LSK cells. DNA methylation sequencing was performed and analyzed using an enhanced reduced representation (ERRBS) methodology as previously described. DNA was extracted from purified LSK cells of 6-month old WT and Tet1 KO mice, Bisulphite treatment was performed using the EZ DNA Methylation Kit (Zymo Research). Libraries were amplified according to illumina protocols and sequenced on an Illumina HiSeq2500 machine DNA methylation profiling of LSK cells in WT and Tet1 KO mice.
2015-04-12 | E-GEOD-65919 | biostudies-arrayexpress
Project description:Cytosine DNA bases can be methylated by DNA methyltransferases and subsequently oxidized by TET proteins. The resulting 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC) are considered demethylation intermediates as well as stable epigenetic marks. To dissect the contribution of these cytosine modifying enzymes, we generated combinations of Tet knockout (KO) embryonic stem cells (ESCs) and systematically measured protein and DNA modification levels at the transition from naive to primed pluripotency. Whereas the increase of genomic 5-methylcytosine (5mC) levels during exit from pluripotency correlated with an upregulation of the de novo DNA methyltransferases DNMT3A and DNMT3B, the subsequent oxidation steps turned out to be far more complex. The strong increase of oxidized cytosine bases (5hmC, 5fC, and 5caC) was accompanied by a drop in TET2 levels, yet the analysis of KO cells suggested that TET2 is responsible for most 5fC formation. The comparison of modified cytosine and enzyme levels in Tet KO cells revealed distinct and differentiation-dependent contributions of TET1 and TET2 to 5hmC and 5fC formation arguing against a processive mechanism of 5mC oxidation. The apparent independent steps of 5hmC and 5fC formation suggest yet to be identified mechanisms regulating TET activity and may constitute another layer of epigenetic regulation.
2020-07-24 | PXD019514 | Pride
Project description:Surveillance 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 understanding of DNA methylation dynamics. Interestingly, in recent years evidence accumulated that TET1 also harbours non-catalytic functions. However, the role and mechanism of TET1 DNA demethylation independent functions still remain poorly understood. Here, we use genome engineering and quantitative multi-omics approaches to dissect the non-catalytic role of TET1. Strikingly, we find that the majority of transcriptional regulation depends on non-catalytic functions of TET1. To gain insights into possible mechanisms by which TET1 regulates transcription independent of DNA demethylation, we asked if the loss of TET1 is accompanied by changes in the histone modificaiton landscape. To this end, we compared the relative abundances of core histone modifications between Tet1 KO, Tet1 CM and WT mESCs using quantitative LC-MS/MS analysis. Surprisingly, we observed a profound global reduction of pH4Kac and H4K20me3 as well as H3K27me3 in Tet1 KO mESC. Vice versa, the monomethylation states of the latter two residues, H3K27me1 and H4K20me1 were significantly increased in Tet1 KO. Similar to the results from the transcriptome data, most of these changes were specific to Tet1 KO cells.
2022-08-11 | PXD028566 | Pride
Project description:Adipose tissue is important for systemic metabolic homeostasis in response to environmental changes, and adipogenesis involves dynamic transcriptional regulation. DNA methylation on cytosine (C) of CpG (5mC) is an abundant epigenetic modification that mediates genomic imprinting and regulates gene expression. TET family enzymes (TET1, TET2 and TET3) oxidize the 5mC in DNA to 5-hydroxylmethylcytosine (5hmC), which associates with transcriptional activation. Through a phenotypic screen, we found TET inhibition decreased adipocyte differentiation from mesenchymal stem cells (MSCs). Comparing with the undifferentiated MSCs, the differentiated adipocytes exhibited much higher levels of 5hmC and slightly increased 5fC and 5caC. Higher 5hmC associated with better differentiation at single cell level. TET1 is upregulated in differentiation and depletion of it significantly impaired the gain of 5hmC. Furthermore, Tet1 depletion significantly hampered the adipocyte differentiation in vitro and adipose tissue maintenance in vivo. Using RNA-seq, 5mC and 5hmC-DNA immunoprecipitation, we found that Tet1 knockout led to decreased expression of genes associated with lipid metabolism and fat cell differentiation. Genes with loss of 5mC or gain of 5hmC in adipocytes include Lipe, Bmp4 and Rxra etc. Rxra is one of the critical TET1 modulated genes for adipose development, as RXRα agonist partially rescued the inhibitory effect of Tet1 knockout. Together, TET1-mediated active DNA demethylation plays an important role in adipose tissue.
2021-06-30 | GSE144644 | GEO
Project description:DNA methylation of C5-cytosine (5mC) in the mammalian genome is a key epigenetic event that is critical for various cellular processes. However, how the genome-wide 5mC pattern is dynamically regulated remains a fundamental question in epigenetic biology. The TET family of 5mC hydroxylases, which convert 5mC to 5-hydroxymethylcytosine (5hmC), have provided a new potential mechanism for the dynamic regulation of DNA methylation. The extent to which individual Tet family members contribute to the genome-wide 5mC and 5hmC patterns and associated gene network remains largely unknown. Here we report genome-wide mapping of Tet1 and 5hmC in mESCs and reveal a mechanism of action by which Tet1 controls 5hmC and 5mC levels in mESCs. In combination with microarray and mRNA-seq expression profiling, we identify a comprehensive yet intricate gene network influenced by Tet1. We propose a model whereby Tet1 controls DNA methylation both by binding to CpG-rich regions to prevent unwanted DNA methyltransferase activity, and by converting the existing 5mC to 5hmC through its enzymatic activity. This Tet1-mediated antagonism of CpG methylation imparts differential maintenance of DNA methylation status at Tet1 target loci, thereby providing a new regulatory mechanism for establishing the epigenetic landscape of mESCs, which ultimately contributes to mESC differentiation and the onset of embryonic development. To determine the genome-wide DNA methylation changes caused by Tet1 depletion in mouse ES cells. Tet1 protein was depleted by specific siRNA treatment. The DNA methylation levels in control and Tet1 siRNA-transfected ES cells were determined by targeted bisulfite sequencing.
2011-04-21 | E-GEOD-28533 | biostudies-arrayexpress