TET1 regulates hypoxia-induced epithelial-mesenchymal transition through DNA demethylation (RNA-Seq)
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE59987 | GEO | 2014/08/01
SECONDARY ACCESSION(S): PRJNA257213
REPOSITORIES: GEO
Similar Datasets
Project description:In order to explore the status of DNA methylation in hypoxia response, we show that TET1, a DNA dioxygenase converting 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC), regulates hypoxia-responsive gene expression. Hypoxia/HIF-2α regulates the expression of TET1. Knockdown of TET1 mitigated hypoxia-induced EMT. RNA sequencing and 5hmC sequencing identified the set of TET1-regulated genes.
2014-08-01 | GSE59989 | GEO
Project description:In order to explore the status of DNA methylation in hypoxia response, we show that TET1, a DNA dioxygenase converting 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC), regulates hypoxia-responsive gene expression. Hypoxia/HIF-2α regulates the expression of TET1. Knockdown of TET1 mitigated hypoxia-induced EMT. RNA sequencing and 5hmC sequencing identified the set of TET1-regulated genes. Four samples (Four samples, Hypoxia (scrambled control), Hypoxia (TET1-si), Normoxia (scrambled control) and Normoxia (TET1-si), are performed by RNA-Seq and hMeDIP-Seq
2014-08-01 | E-GEOD-59989 | biostudies-arrayexpress
Project description:In order to explore the status of DNA methylation in hypoxia response, we show that TET1, a DNA dioxygenase converting 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC), regulates hypoxia-responsive gene expression. Hypoxia/HIF-2α regulates the expression of TET1. Knockdown of TET1 mitigated hypoxia-induced EMT. RNA sequencing and 5hmC sequencing identified the set of TET1-regulated genes. Four samples (Four samples, Hypoxia (scrambled control), Hypoxia (TET1-si), Normoxia (scrambled control) and Normoxia (TET1-si), are performed by RNA-Seq and hMeDIP-Seq RNA-Seq and hMeDIP-Seq
2014-08-01 | E-GEOD-59987 | biostudies-arrayexpress
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: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 | GSE144613 | GEO
Project description:We report that full length TET1 (TET1-FL) overexpression fails to induce global DNA demethylation in HEK293T cells. The preferential binding of TET1-FL to hypomethylated CpG islands (CGIs) through its CXXC domain leads to its inhibited 5-hydroxymethylcytosine (5hmC) production as methylation level increases. TET1-FL-induced 5hmC accumulates at CGI edges, while TET1 knockdown induces methylation spreading from methylated edges into hypomethylated CGIs. However, TET1 can regulate gene transcription independent of its dioxygenase catalytic function. Thus, our results identify TET1 as a maintenance DNA demethylase that does not purposely decrease methylation levels, but specifically maintains the DNA hypomethylation state of CGIs in adult cells. hMeDIP-seq analysis of genomic 5-hydroxymethylcytosine in HEK293T cells overexpressing mTET1-CD, TET1-CD, mTET1-FL, or TET1-FL
2014-06-04 | E-GEOD-44036 | biostudies-arrayexpress
Project description:We report that full length TET1 (TET1-FL) overexpression fails to induce global DNA demethylation in HEK293T cells. The preferential binding of TET1-FL to hypomethylated CpG islands (CGIs) through its CXXC domain leads to its inhibited 5-hydroxymethylcytosine (5hmC) production as methylation level increases. TET1-FL-induced 5hmC accumulates at CGI edges, while TET1 knockdown induces methylation spreading from methylated edges into hypomethylated CGIs. However, TET1 can regulate gene transcription independent of its dioxygenase catalytic function. Thus, our results identify TET1 as a maintenance DNA demethylase that does not purposely decrease methylation levels, but specifically maintains the DNA hypomethylation state of CGIs in adult cells. Genome-wdie profiling of gene expression in HEK293T cells following overexpression of wild type or catalytically mutant TET1-FL or TET1-CD
2014-06-04 | E-GEOD-49833 | biostudies-arrayexpress
Project description:We report that full length TET1 (TET1-FL) overexpression fails to induce global DNA demethylation in HEK293T cells. The preferential binding of TET1-FL to hypomethylated CpG islands (CGIs) through its CXXC domain leads to its inhibited 5-hydroxymethylcytosine (5hmC) production as methylation level increases. TET1-FL-induced 5hmC accumulates at CGI edges, while TET1 knockdown induces methylation spreading from methylated edges into hypomethylated CGIs. However, TET1 can regulate gene transcription independent of its dioxygenase catalytic function. Thus, our results identify TET1 as a maintenance DNA demethylase that does not purposely decrease methylation levels, but specifically maintains the DNA hypomethylation state of CGIs in adult cells. HEK293T cells were transfected with wild type or catalytically mutant TET1 expression plasmids (TET1-CD, mTET1-CD, TET1-FL and mTET1-FL), or subjected to shRNA-mediated TET1 knockdown. Total RNA samples were extracted and assayed on Affymetrix microarrays
2014-06-04 | E-GEOD-50016 | biostudies-arrayexpress
Project description:Epigenetic pathways that regulate DNA methylation and chromatin modifications are frequently found to be dysregulated in human cancers. The TET methylcytosine dioxygenase 1 (TET1) enzyme is an important regulator of hydroxymethylcytosine (5hmC) in embryonic stem cells, neural progenitors,adult cells and reprogrammed cells. Decreased expression of TET proteins and loss of 5hmC has been reported in many tumors, suggesting a critical role for the maintenance of this epigenetic modification in normal cellular function. However, loss of TET1 function in the etiology of cancer has not been directly investigated. Here, we show that deletion of the Tet1 gene promotes the development of B cell lymphoma. Tet1 is required for maintaining normal levels of 5hmC, preventing aberrant DNA hypermethylation and for the regulation of transcriptional programs involved in B-cell lineage specification, chromosome maintenance, and DNA repair. Progenitor B cells in the absence of Tet1 accumulate DNA damage and whole-exome sequencing of Tet1-deficient tumors revealed a high correlation of mutations with those most frequently found in Non-Hodgkin B cell lymphoma (B-NHL) patients. In addition, we show that the TET1 gene is deleted, hypermethylated and transcriptionally silenced in B-NHL patients. These findings provide the first in vivo evidence of TET1 function as a tumor suppressor of hematopoietic malignancy. We did hydroxymethylation tests for two wild type mice and two Tet1 knockout mice.
2015-04-12 | E-GEOD-65895 | biostudies-arrayexpress