DNA methylatioin analysis of breast cancer cell lines with TET1 knockout
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA475775 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR5768010_1.fastq.gz | Fastqsanger.gz | |||
| SRR5768010_2.fastq.gz | Fastqsanger.gz | |||
| SRR5768020_1.fastq.gz | Fastqsanger.gz | |||
| SRR5768020_2.fastq.gz | Fastqsanger.gz | |||
| SRR5768030_1.fastq.gz | Fastqsanger.gz |
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Project description:Both gains and losses of DNA methylation are common in cancer but the factors controlling this methylation balance remain unclear. Triple negative breast cancer (TNBC), a subtype that does not overexpress hormone receptors or HER2/NEU is one of the most hypomethylated cancers observed. In search for an explanation for this, we discovered that the TET1 DNA demethylase is specifically overexpressed in about 40% of patients with TNBC, where it is associated with hypomethylation of up to 10% of queried CpG sites and a worse overall survival. Through bioinformatic analyses in both breast and ovarian cancer cell line panels, we uncovered an intricate network connecting TET1 to hypomethylation and activation of cancer specific oncogenic pathways including PI3K, EGFR and PDGF. TET1 expression correlated with sensitivity to drugs targeting the PI3K-mTOR pathway. CRISPR mediated deletion of TET1 in two independent TNBC cell lines resulted in reduced expression of PI3K pathway genes, upregulation of immune response genes and substantially reduced cellular proliferation, suggesting dependence of oncogenic pathways on TET1 overexpression. Our work establishes TET1 as a potential oncogene that contributes to aberrant hypomethylation in cancer and suggests that TET1 could serve as a novel druggable target for therapeutic intervention.
2018-06-28 | GSE115685 | GEO
Project description:DNA methylation analysis of breast cancer Hs578T cells with TET1 knockout
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Project description:Both gains and losses of DNA methylation are common in cancer but the factors controlling this methylation balance remain unclear. Triple negative breast cancer (TNBC), a subtype that does not overexpress hormone receptors or HER2/NEU is one of the most hypomethylated cancers observed. In search for an explanation for this, we discovered that the TET1 DNA demethylase is specifically overexpressed in about 40% of patients with TNBC, where it is associated with hypomethylation of up to 10% of queried CpG sites and a worse overall survival. Through bioinformatic analyses in both breast and ovarian cancer cell line panels, we uncovered an intricate network connecting TET1 to hypomethylation and activation of cancer specific oncogenic pathways including PI3K, EGFR and PDGF. TET1 expression correlated with sensitivity to drugs targeting the PI3K-mTOR pathway. CRISPR mediated deletion of TET1 in two independent TNBC cell lines resulted in reduced expression of PI3K pathway genes, upregulation of immune response genes and substantially reduced cellular proliferation, suggesting dependence of oncogenic pathways on TET1 overexpression. Our work establishes TET1 as a potential oncogene that contributes to aberrant hypomethylation in cancer and suggests that TET1 could serve as a novel druggable target for therapeutic intervention.
2018-06-26 | GSE115578 | GEO
Project description:Global gene expression profile of Tet1 knockout ES cells is compared to wild-type ES cells. All ES lines used are V6.5 (mix 129 C57BL6 backgound). 2 Tet1 KO mice compared to 1 Tet1 wild type mouse.
2011-07-31 | E-GEOD-30748 | biostudies-arrayexpress
Project description:DNA hypermethylation is known to contribute to the formation of cancer. However, DNA hypomethylation has received far less attention and the factors controlling the balance between hypo and hypermethylation and its impact on tumorigenesis remains unclear. Triple negative breast cancer (TNBC), a subtype of breast cancer that does not overexpress the hormone receptors or HER2/NEU, is one of the most hypomethylated cancers observed. Importantly, TNBCs are often a therapeutic challenge because of advanced presentation and lack of targeted therapies. TET1 is a DNA demethylase that regulates DNA methylation, hydroxymethylation and gene expression. We found that TET1 is specifically overexpressed in TNBC, where it is associated with hypomethylation and a worse overall survival. Further, we uncover an intricate network connecting TET1 expression to maintaining activation of cancer specific pathways, including PI3K, EGFR and PDGF. In TET1 KO cells, we observed reduced phospho-4EBP1 and decreased expression of genes in the PI3K pathway, suggesting loss of PI3K-mTOR activity is concomitant with loss of TET1. Additionally, TET1 KO cells have reduced cellular proliferation and migration. Our work establishes TET1 as an oncogene that contributes to the aberrant hypomethylation observed in cancer and suggests TET1 could serve as a novel druggable target for therapeutic intervention.
2018-06-28 | GSE100640 | GEO
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:Dissection of catalytic and non-catalytic functions of Tet1. DNA methylation (RRBS) profiling of wild type, Tet1 knockout and catalytic mutants during EpiLC differentiation.
2020-09-30 | E-MTAB-6785 | biostudies-arrayexpress
Project description:DNA hypermethylation is known to contribute to the formation of cancer. However, DNA hypomethylation has received far less attention and the factors controlling the balance between hypo and hypermethylation and its impact on tumorigenesis remains unclear. Triple negative breast cancer (TNBC), a subtype of breast cancer that does not overexpress the hormone receptors or HER2/NEU, is one of the most hypomethylated cancers observed. Importantly, TNBCs are often a therapeutic challenge because of advanced presentation and lack of targeted therapies. TET1 is a DNA demethylase that regulates DNA methylation, hydroxymethylation and gene expression. We found that TET1 is specifically overexpressed in TNBC, where it is associated with hypomethylation and a worse overall survival. Further, we uncover an intricate network connecting TET1 expression to maintaining activation of cancer specific pathways, including PI3K, EGFR and PDGF. In TET1 KO cells, we observed reduced phospho-4EBP1 and decreased expression of genes in the PI3K pathway, suggesting loss of PI3K-mTOR activity is concomitant with loss of TET1. Additionally, TET1 KO cells have reduced cellular proliferation and migration. Our work establishes TET1 as an oncogene that contributes to the aberrant hypomethylation observed in cancer and suggests TET1 could serve as a novel druggable target for therapeutic intervention.
2018-06-26 | GSE100483 | GEO
Project description:TET1 knockdown cancer cell lines
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Project description:Global gene expression profile of Tet1 knockout ES cells is compared to wild-type ES cells. All ES lines used are V6.5 (mix 129 C57BL6 backgound).
2011-08-01 | GSE30748 | GEO