Tet1 is a tumor suppressor of hematopoietic maligancy [RRBS]
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE65919 | GEO | 2015/04/12
SECONDARY ACCESSION(S): PRJNA275404
REPOSITORIES: GEO
Similar Datasets
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: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: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 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.
2015-04-12 | GSE65955 | 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: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: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
Project description:Tet enzymes (Tet1/2/3) convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). Tet1 and Tet2 mediate 5hmC generation in mouse embryonic stem cells (ESCs) and various embryonic and adult tissues. To investigate the effects of combined deficiency of Tet1 and Tet2 on pluripotency and development, we have generated Tet1 and Tet2 double knockout (DKO) ESCs and mice. DKO ESCs were depleted of 5hmC, but remained pluripotent with subtle defects in differentiation and changes in gene expression. Double mutant embryos and chimeras exhibited mid-gestation defects and postnatal DKO mice displayed partially penetrant neonatal lethality and stochastic perturbation of imprinting. Viable DKO animals developed normally to adulthood but had reduced 5hmC level, increased 5mC level and lacked 5hmC in germ cells. Nevertheless, DKO mice of both sexes were fertile with females having smaller ovaries and reduced fertility. Our data suggest that both Tet1 and Tet2 contribute to 5hmC levels during development. Their combined loss does not block differentiation and embryogenesis, but leads to partially penetrant embryonic and perinatal abnormalities and compromised viability. Moreover, the presence of substantial levels of 5hmC in DKO embryos and adult mice suggests a significant contribution of Tet3 in hydroxylation of 5mC during development. Methylation patterns in tissue samples from a series of wt and Tet1/Tet2 DKO embryos, neonates and adults were generated using methylated DNA immunoprecipitation with antibodies against 5mC (MeDIP) and 5hmC (hMeDIP) followed by deep sequencing.
2013-02-01 | E-GEOD-42396 | biostudies-arrayexpress
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. Tet1 protein was depleted in J1 or E14 mouse ES cells by siRNA or shRNA treatment. Total RNA was purified and used to determine the global gene transcription profiles by microarray assays. The Tet1-regulated genes were identified by comparing the gene expression profiles of control and Tet1-depleted ES cells.
2011-04-21 | E-GEOD-28530 | biostudies-arrayexpress