Analysis of gene expression in TET1 depleted colorectal cancer Colo320DM cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE84396 | GEO | 2017/01/01
SECONDARY ACCESSION(S): PRJNA329081
REPOSITORIES: GEO
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Project description:We aimed to analyze the relationship between TET1 and aberrant CpG methylation in colorectal cancer (CRC). We established three stable TET1 knockdown clones and negative control clones of Colo320DM cells, and carried out DNA methylation analysis with HumanMethylation450 BeadChip.
2017-01-01 | GSE84397 | GEO
Project description:We aimed to analyze the relationship between TET1 and aberrant CpG methylation in colorectal cancer (CRC). We established two stable TET1 knockdown clones and negative control clones of HCT116 cells, and carried out gene expression analysis with Agilent Human Gene Expression microarray kit.
2017-01-01 | GSE84398 | GEO
Project description:We aimed to analyze the relationship between TET1 and aberrant CpG methylation in colorectal cancer (CRC). We established two stable TET1 knockdown clones and negative control clones of HCT116 cells, and carried out DNA methylation analysis with HumanMethylation450 BeadChip.
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Project description:Cancer-associated fibroblasts (CAFs) are an important component of the desmoplastic stroma in rectal cancer. Preoperative chemoradiotherapy plays a pivotal role in the management of locally advanced rectal cancer. Patient-derived CAFs were used to evaluate the response to radiotherapy and its consequent impact on colorectal cancer cells (COLO320DM). COLO320DM cells were seeded and 24 hours later 1.8Gy irradiated. Subsequently, 24h later COLO320DM cells were treated with the secretome of 10x 1.8Gy irradiated CAFs or sham treated CAFs in 0.5% of serum. RNA was isolated 6 hours or 48 hours later.
2017-11-01 | E-MTAB-5364 | biostudies-arrayexpress
Project description:TET1 oxidizes methylated cytosine into 5-hydroxymethylcytosine, resulting in regulation of DNA methylation and gene expression. Full length TET1 (TET1-FL) has a CXXC domain that binds to unmethylated stretches of CpG dinucleotides known as CpG islands (CGIs). This CXXC domain allows TET1 to protect CGIs from aberrant methylation but it also limits its ability to regulate genes outside of CGIs. Here we report a novel isoform of TET1 (TET1-ALT) that has a unique transcription start site from an alternate promoter in intron 2, yielding a protein with a unique translation start site. Importantly, TET1-ALT lacks the CXXC domain but retains the catalytic domain. To identify the gene expression targets of TET1-ALT and to compare them to the gene expression targets of TET1-FL, we performed RNA-seq on HEK293T cells that overexpress either Empty Vector (Control), TET1-FL or TET1-ALT.
2017-05-12 | GSE93619 | GEO
Project description:Aberrant DNA methylation is frequent in colorectal cancer (CRC), but the underlying mechanisms and pathological consequences are poorly understood. Ten-Eleven Translocation (TET) dioxygenases and Thymine DNA Glycosylase (TDG) mediate active DNA demethylation by generating and removing oxidized cytosine species. TET1 and TDG mutations, and altered levels of oxidized cytosines have been identified in human CRC. To investigate the TET-TDG demethylation axis in intestinal tumorigenesis, we generated ApcMin mice that are devoid of Tet1 and/or Tdg, and characterized the methylome and transcriptome of intestinal adenomas. There were increased numbers (>30) of adenomas in ApcMin mice expressing the dominant-negative TdgN151A allele, whereas Tet1-deficient and Tet1/Tdg-double heterozygous ApcMin adenomas were larger and displayed features of erosion and invasion. Methylome analysis revealed reduction in global DNA hypomethylation in colonic adenomas from Tet1- and Tdg-mutant ApcMin mice, and hypermethylation of CpG islands in Tet1-mutant ApcMin mice. In addition, RNA sequencing showed upregulation of inflammatory, immune and interferon response genes in Tet1- and Tdg-mutant colonic adenomas compared to control ApcMin adenomas. The corresponding 127-gene inflammatory signature separated human colonic adenocarcinomas in four groups, closely aligned with their microsatellite or chromosomal instability, and characterized by different levels of DNA methylation and DNMT1 expression that anti-correlated with TET1 expression. These findings demonstrate a novel mechanism of epigenetic regulation during intestinal tumorigenesis by which TET1-TDG-mediated DNA demethylation may decrease methylation levels and inflammatory/interferon/immune responses, and is linked to the type of genomic instability.
2024-07-01 | GSE179313 | 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:Aberrant DNA methylation is frequently observed in colorectal cancer (CRC), but the underlying mechanisms and pathological consequences are poorly understood. Ten-Eleven Translocation (TET) dioxygenases and Thymine DNA Glycosylase (TDG) are involved in active DNA demethylation by generating and removing novel oxidized cytosine species. TET1 and TDG mutations, and alterations of the levels of oxidized cytosines have been identified in human CRC. To clarify the biological significance of the TET-TDG demethylation axis in intestinal tumorigenesis, we generated ApcMin mice that are devoid of Tet1 and/or Tdg, and characterized the methylome and transcriptome of intestinal adenomas by DREAM and RNA sequencing, respectively. Tet1-deficient and Tet1/Tdg-double heterozygous ApcMin adenomas manifested increased adenoma size and features of erosion or invasion, whereas an increased number (>30) of adenomas was found in Tdg-mutant ApcMin mice. Methylome analysis revealed progressive loss of global DNA hypomethylation in colonic adenomas from Tet1- and Tdg-deficient ApcMin mice, and hypermethylation of CpG islands in Tet1-deficient ApcMin mice. In addition, RNA sequencing showed upregulation of genes in inflammatory, immune and interferon response in Tet1- and Tdg-mutant colonic adenomas compared to control ApcMin adenomas. The corresponding 135-gene inflammatory signature separated human colonic adenocarcinomas into four groups, closely aligned with their microsatellite or chromosomal instability profile, and characterized by different levels of DNA methylation and DNMT1 expression levels that anti-correlated with TET1 expression levels. These findings demonstrate a novel mechanism of epigenetic regulation during intestinal tumorigenesis by which TET1-TDG-mediated active DNA demethylation decreases not only methylation levels, but also inflammatory/interferon/immune response, which impinges on the intrinsic features of genomic instability of the tumors. This study establishes a novel link, via inflammatory response, between epigenomic and genomic instability.
2023-10-01 | GSE179526 | GEO
Project description:TET1 maintains hypomethylation at bivalent promoters through its catalytic activity in embryonic stem cells (ESCs). However, whether and how TET1 exerts catalytic activity-independent functions in regulating bivalent genes is not well understood. Therefore, we mapped the TET1 interactome in mouse ESCs using a SILAC IP-MS proteomics approach.
2022-06-10 | PXD033587 | Pride
Project description:Epigenetic modification of the mammalian genome by DNA methylation (5-methylcytosine) has a profound impact on chromatin structure, gene expression and maintenance of cellular identity. Recent demonstration that members of the Ten-eleven translocation (Tet) family proteins can convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) raised the possibility that Tet proteins are capable of establishing a distinct epigenetic state. We have recently demonstrated that Tet1 is specifically expressed in murine embryonic stem (ES) cells and is required for ES cell self-renewal and maintenance. Using chromatin immunoprecipitation coupled with high-throughput DNA sequencing (ChIP-seq), here we show that Tet1 is preferentially bound to CpG-rich sequences at promoters of both transcriptionally active and Polycomb-repressed genes. Despite a general increase in levels of DNA methylation at Tet1 binding-sites, Tet1 depletion does not lead to down-regulation of all the Tet1 targets. Interestingly, while Tet1-mediated promoter hypomethylation is required for maintaining the expression of a group of transcriptionally active genes, it is also required for repression of Polycomb-targeted developmental regulators. Tet1 contributes to silencing of this group of genes by facilitating recruitment of PRC2 to CpG-rich gene promoters. Thus, our study not only establishes a role for Tet1 in modulating DNA methylation levels at CpG-rich promoters, but also reveals a dual function of Tet1 in promoting transcription of pluripotency factors as well as participating in the repression of Polycomb-targeted developmental regulators. Mouse ES cells infected with control knockdown (KD) or Tet1 KD lentiviruses were FACS-sorted for RNA extraction and hybridization on Affymetrix microarrays. We also investigated the effect of Nanog overexpression (OE) in Tet1 KD mouse ES cells on dys-regulated Tet1 targets. We have collected four biologically independent replicates for each treatment.
2011-03-30 | E-GEOD-26830 | biostudies-arrayexpress