Effect of TET1 overexpression on hydroxymethylcytosine levels of HEK293 cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE67621 | GEO | 2015/07/16
SECONDARY ACCESSION(S): PRJNA280500
REPOSITORIES: GEO
Similar Datasets
Project description:We compared TET1 overexpressing cells to uninduced cells with endogenous TET1 transcript levels to determine DNA methylation changes.
2015-07-16 | GSE67349 | GEO
Project description:We compared TET1 overexpressing cells to uninduced cells with endogenous TET1 transcript levels to determine DNA methylation changes. TET1 overexpression
2015-07-16 | E-GEOD-67349 | biostudies-arrayexpress
Project description:We compared TET1 and TET3 overexpressing cells to uninduced cells with endogenous levels of the respective transcript to determine global gene expression changes.
2015-07-16 | GSE39186 | GEO
Project description:We compared TET1 and TET3 overexpressing cells to uninduced cells with endogenous levels of the respective transcript to determine global gene expression changes. TET1 overexpression, TET3 overexpression
2015-07-16 | E-GEOD-39186 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE34886: Acute depletion of Tet1-dependent 5-hydroxymethylcytosine levels impairs LIF/Stat3 signaling and results in loss of embryonic stem cell identity [expression profiling] GSE34887: Acute depletion of Tet1-dependent 5-hydroxymethylcytosine levels impairs LIF/Stat3 signaling and results in loss of embryonic stem cell identity [MRE-seq] Refer to individual Series
2012-01-04 | E-GEOD-34267 | 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. 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: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:The TET family of FE(II) and 2-oxoglutarate-dependent enzymes (Tet1/2/3) promote DNA demethylation by converting 5-methylcytosine to 5-hydroxymethylcytosine (5hmC), which they further oxidize into 5-formylcytosine and 5-carboxylcytosine. Tet1 is robustly expressed in mouse embryonic stem cells (mESCs) and has been implicated in mESC maintenance. Here we demonstrate that, unlike genetic deletion, RNAi-mediated depletion of Tet1 in mESCs led to a significant reduction in 5hmC and loss of mESC identity. The differentiation phenotype due to Tet1 depletion positively correlated with the extent of 5hmC loss. Meta-analyses of genomic datasets suggested interaction between Tet1 and leukemia inhibitory factor (LIF) signaling. LIF signaling is known to promote self-renewal and pluripo-tency in mESCs partly by opposing MAPK/ERK mediated differentiation. Withdrawal of LIF leads to differentiation of mESCs. We discovered that Tet1 depletion impaired LIF-dependent Stat3-mediated gene activation by affecting Stat3's ability to bind to its target sites on chromatin. Nanog overexpression or inhibition of MAPK/ERK signaling, both known to maintain mESCs in the absence of LIF, rescued Tet1 depletion, further supporting the dependence of LIF/Stat3 signaling on Tet1. These data support the conclusion that analysis of mESCs in the hours/days immediately following efficient Tet1 depletion reveals Tet1’s normal physiological role in maintaining the pluripotent state that may be subject to homeostatic compensation in genetic models. Genome-wide mapping of 5hmC and microarray gene expression profiling in E14Tg2a mESCs after transfection with indicated siRNAs: Tet1 siRNA #1 (Invitrogen, MSS284895), Tet1 siRNA #2 (Invitrogen, MSS284897), and Control siRNA duplex targeting firefly luciferase.
2012-01-06 | E-GEOD-34887 | biostudies-arrayexpress
Project description:The TET family of FE(II) and 2-oxoglutarate-dependent enzymes (Tet1/2/3) promote DNA demethylation by converting 5-methylcytosine to 5-hydroxymethylcytosine (5hmC), which they further oxidize into 5-formylcytosine and 5-carboxylcytosine. Tet1 is robustly expressed in mouse embryonic stem cells (mESCs) and has been implicated in mESC maintenance. Here we demonstrate that, unlike genetic deletion, RNAi-mediated depletion of Tet1 in mESCs led to a significant reduction in 5hmC and loss of mESC identity. The differentiation phenotype due to Tet1 depletion positively correlated with the extent of 5hmC loss. Meta-analyses of genomic datasets suggested interaction between Tet1 and leukemia inhibitory factor (LIF) signaling. LIF signaling is known to promote self-renewal and pluripo-tency in mESCs partly by opposing MAPK/ERK mediated differentiation. Withdrawal of LIF leads to differentiation of mESCs. We discovered that Tet1 depletion impaired LIF-dependent Stat3-mediated gene activation by affecting Stat3's ability to bind to its target sites on chromatin. Nanog overexpression or inhibition of MAPK/ERK signaling, both known to maintain mESCs in the absence of LIF, rescued Tet1 depletion, further supporting the dependence of LIF/Stat3 signaling on Tet1. These data support the conclusion that analysis of mESCs in the hours/days immediately following efficient Tet1 depletion reveals Tet1M-bM-^@M-^Ys normal physiological role in maintaining the pluripotent state that may be subject to homeostatic compensation in genetic models. Genome-wide mapping of 5hmC and microarray gene expression profiling in E14Tg2a mESCs after transfection with indicated siRNAs: Tet1 siRNA #1 (Invitrogen, MSS284895), Tet1 siRNA #2 (Invitrogen, MSS284897), and Control siRNA duplex targeting firefly luciferase.
2012-01-06 | E-GEOD-34886 | biostudies-arrayexpress
Project description:The TET family of FE(II) and 2-oxoglutarate-dependent enzymes (Tet1/2/3) promote DNA demethylation by converting 5-methylcytosine to 5-hydroxymethylcytosine (5hmC), which they further oxidize into 5-formylcytosine and 5-carboxylcytosine. Tet1 is robustly expressed in mouse embryonic stem cells (mESCs) and has been implicated in mESC maintenance. Here we demonstrate that, unlike genetic deletion, RNAi-mediated depletion of Tet1 in mESCs led to a significant reduction in 5hmC and loss of mESC identity. The differentiation phenotype due to Tet1 depletion positively correlated with the extent of 5hmC loss. Meta-analyses of genomic datasets suggested interaction between Tet1 and leukemia inhibitory factor (LIF) signaling. LIF signaling is known to promote self-renewal and pluripo-tency in mESCs partly by opposing MAPK/ERK mediated differentiation. Withdrawal of LIF leads to differentiation of mESCs. We discovered that Tet1 depletion impaired LIF-dependent Stat3-mediated gene activation by affecting Stat3's ability to bind to its target sites on chromatin. Nanog overexpression or inhibition of MAPK/ERK signaling, both known to maintain mESCs in the absence of LIF, rescued Tet1 depletion, further supporting the dependence of LIF/Stat3 signaling on Tet1. These data support the conclusion that analysis of mESCs in the hours/days immediately following efficient Tet1 depletion reveals Tet1’s normal physiological role in maintaining the pluripotent state that may be subject to homeostatic compensation in genetic models.
2012-01-06 | GSE34887 | GEO