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貨期:
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用途:
For Research Use Only. Not for use in diagnostic or therapeutic procedures.
Dioxygenase that catalyzes the conversion of the modified genomic base 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC) and plays a key role in active DNA demethylation. Also mediates subsequent conversion of 5hmC into 5-formylcytosine (5fC), and conversion of 5fC to 5-carboxylcytosine (5caC). In addition to its role in DNA demethylation, plays a more general role in chromatin regulation by recruiting histone modifying protein complexes to alter histone marks and chromatin accessibility, leading to both activation and repression of gene expression. Plays therefore a role in many biological processes and diseases, including stem cell maintenance, T and B-cell development, inflammation regulation, genomic imprinting, neural activity or DNA repair. Involved in the balance between pluripotency and lineage commitment of cells it plays a role in embryonic stem cells maintenance and inner cell mass cell specification. Plays an important role in the tumorigenicity of glioblastoma cells. TET1-mediated production of 5hmC acts as a recruitment signal for the CHTOP-methylosome complex to selective sites on the chromosome, where it methylates H4R3 and activates the transcription of genes involved in glioblastomagenesis. Binds preferentially to DNA containing cytidine-phosphate-guanosine (CpG) dinucleotides over CpH (H=A, T, and C), hemimethylated-CpG and hemimethylated-hydroxymethyl-CpG. Plays an essential role in the protection and maintenance of transcriptional and developmental programs together with QSER1 to inhibit the binding of DNMT3A/3B and therefore de novo methylation.
基因功能參考文獻:
Our study demonstrates the existence of a TET1/DUOX2/ROS/EMT axis that could play a role in colon cancer chemo-resistance and the aggressiveness of this cancer. PMID: 29715584
this study illustrates the involvement of TET1 in the different arms of the DNA damage response (DDR) and suggests its loss results in the continued survival of cells with genomic instability PMID: 28758831
Data show that knockdown of STAT transcription factors STAT3 and/or STAT5 reduces DNA methylcytosine dioxygenase Ten-eleven translocation 1 (TET1) level. PMID: 29235481
data demonstrated that miR4284 could promote tumor cell growth, migration and invasion by directly targeting TET1 in gastric cancer, which may provide a potential therapeutic target for gastric cancer treatment. PMID: 29512746
Low TET1 expression is associated with colorectal cancer. PMID: 29549908
These data indicate that AA has the potential to modify TET function in lymphoma and enhance chemosensitivity. In addition, the AA deficiency seen in some patients may further impair TET function and contribute to resistance. Clinical trials testing intravenous AA with chemotherapy are warranted. PMID: 28731456
Infrequent occurrence of TET1, TET3, and ASXL2 mutations in myelodysplastic/myeloproliferative neoplasms. PMID: 29531217
the findings of this study indicate that miR27a3p is upregulated, while TET1 is downregulated in human osteosarcoma cells PMID: 29484426
TET1 gene expression might serve as a reliable predictor for patients survival in acute myeloid leukemia. PMID: 29402726
expressed in trophoblast cell columns of first-trimester placentas PMID: 29108636
Study provides evidence that low-expression of TET1 in oral squamous cell carcinoma (OSCC) stem cells may stimulate MGMT promoter methylation, while inhibiting MGMT mRNA expression, which ultimately strengthens the sensitivity of OSCC stem cells in regards to chemotherapeutics. PMID: 28643947
TET1 exerts its tumor suppressor function by regulating autophagy in glioma. PMID: 28341638
TET1 expression levels were significantly elevated in EGFR mutant samples (P=0.007). Patients with higher TET1 levels showed a trend of better response rates to EGFR inhibitors compared to low TET1 staining levels, although the result was not significant (P=0.08). PMID: 28776568
Although DNA methylation (5mC) and hydroxymethylation (5hmC) are highly dynamic during early embryonic development, less is known about their roles at later stages of differentiation. 5hmC marks HNF4A promoter 1 previous to terminal hepatocyte differentiation. TET1-dependent 5hmC is required to activate promoter 1-driven HNF4A expression. PMID: 28648900
Study comprehensively examined TET1 expression and methylation status in multiple tumors, and demonstrated that promoter CpG methylation is a predominant mechanism for TET1 inactivation in human cancers. TET1 as a tumor suppressor and CpG demethylase in tumor cells requires its intact catalytic domain, which provides new insight into the epigenetic master role of TET1 in tumor pathogenesis. PMID: 27225590
our findings demonstrate that 5-hmC loss is an epigenetic hallmark of hepatocellular carcinoma , and miR-29a is an important epigenetic modifier, promoting HCC metastasis through TET-SOCS1-MMP9 axis silencing. The results offer a new strategy for epigenetic cancer therapy PMID: 28661477
a mechanism how L1 elements get activated in the absence of Mecp2 PMID: 28524723
Data show that ten-eleven translocation 1 (TET1) suppresses tumor cell growth, migration and invasion through demethylation of CpG island in PTEN promoter by increasing 5-hmC content. PMID: 27121319
Data show that low TET1 mRNA levels were significantly associated with worse metastases-free survival. PMID: 27014907
TET1 binds to tumor suppressor promoters and induces their re-expression through active DNA demethylation. PMID: 27346347
Loss of TET1 expression facilitates colon cancer cell migration via H3K27me3-mediated repression of E-cadherin expression. PMID: 28513825
TET1 potently inhibited canonical Wnt/beta-catenin signaling by demethylating and upregulating two upstream antagonists of this pathway, SFRP2 and DKK1, which was associated with inhibition of EMT and cancer cell metastasis. PMID: 28851501
Data suggest that the predominantly activated isoform of tet oncogene 1 protein (TET1) in cancer cells does not protect from unmethylated CpG islands (CGIs) methylation and likely mediates dynamic site-specific demethylation outside of CGIs. PMID: 28531272
MBD1 regulates localization and activity of Tet1 in a CXXC3 domain-dependent manner. PMID: 28449087
Compared to normal tissues, the expression level of TET1 in colorectal cancer (CRC) was significantly lower. Moreover, in vitro studies showed that TET1 could inhibit cell growth and promote cell metastasis and invasion.TET1 played a multifaceted role in the pathogenesis of CRC, and thereby resulting in multiple effects on tumor progression. PMID: 27846738
In this study, we show that hypercholesterolemia increases the incidence and pathologic severity of colorectal neoplasia in two independent mouse models. Hypocholesterolemia induced an oxidant stress-dependent increase in miR101c, which downregulated Tet1 in hematopoietic stem cells (HSC), resulting in reduced expression of genes critical to natural killer T cell (NKT) and gamma delta T-cell differentiation PMID: 28249902
miR-29b targets the DNA-demethylating enzyme, TET1, for downregulation resulting in decreased 5-hmC epigenetic modifications. PMID: 26776158
The results of the present study demonstrate that TET1 might function as one of the key molecules in SOD3 expression through its 5mC hydroxylation in A549 cells. PMID: 28351182
Results show that the levels of TET1 transcript are elevated in medulloblastoma and ependymoma cells may imply that this protein is involved in pathogenesis of the paediatric brain tumours via demethylation of the regulatory elements of the oncogenes promoting initiation and/or progression of these types of cancer. PMID: 28228863
Loss of TET1 may induce aberrant DNA methylation and may attenuate the effect of 5-aza-2'-deoxycytidine in colorectal cancer cells. PMID: 27977763
our findings reveal that TET1 forms a complex with hMOF to modulate its function and the level of H4K16Ac ultimately affect gene expression and DNA repair. PMID: 27733505
FOXA1 is not only able to recognize but also remodel the epigenetic signatures at lineage-specific enhancers, which is mediated, at least in part, by a feed-forward regulatory loop between FOXA1 and TET1. PMID: 27257062
that miR-30a could inhibit TET1 expression through base pairing with complementary sites in the 3'untranslated region to regulate Drp-1 promoter hydroxymethylation. PMID: 28294974
Increased TET1 induced re-expression of vimentin through active DNA demethylation, and cause partial epithelial-to-mesenchymal (EMT) in A2780 cells. PMID: 28150354
these findings suggest that Tet1 expression plays a critical role in metastasis of lung cancer cells by suppression of invasion and epithelial-mesenchymal transition (EMT). PMID: 26931431
TET regulates gene expression in differentiating colonocytes. PMID: 26631571
expression in systemic sclerosis fibroblasts abnormally regulated in hypoxic environment and accompanied by global DNA hypomethylation PMID: 26013976
Noncovalent binding of ADP-ribose polymers with TET1 catalytic domain decreases TET1 hydroxylase activity while the covalent PARylation stimulates TET1 enzyme. In addition, TET1 activates PARP-1/ARTD1 independently of DNA breaks. PMID: 26136340
Expression levels of TET1 are low in renal carcinoma, particularly in high grade tumors. PMID: 26165803
our study demonstrated that DNA hypomethylation at the TET1 promoter was associated with childhood asthma in African Americans. PMID: 26684294
these data show that hypoxia-inducible genes are regulated in a multilayered manner that includes epigenetic regulation via TETs and 5-hmC levels in addition to HIF stabilization. PMID: 26703470
Identify of MLL-fusion/MYC dash, verticalmiR-26 dash, verticalTET1 signaling circuit in MLL-rearranged acute myeloid leukemia. PMID: 26791235
The expression (mRNA and protein levels) of DNMT1 and TET1 is increased in PFC of SZ and BP disorder patients. PMID: 25476119
these data suggest a dual function of GADD45a in oxidative DNA demethylation, to promote directly or indirectly TET1 activity and to enhance subsequent 5-formylcytosine/5-carboxylcytosine removal. PMID: 26546041
The downregulation of ALDOB could indicate a poor prognosis for HCC patients. In addition, ALDOB inhibits the invasive features of cell lines partly through TET1 expression. PMID: 26376879
Our study indicates that early breast cancer patients with decreased expression of TET1 mRNA had worse overall survival. PMID: 26207381
Aberrant TET1 Methylation is closely Associated with CpG Island Methylator Phenotype in Colorectal Cancer PMID: 26063725
Hypoxia deregulates TET1. TET1/3 levels were associated with tumor hypoxia, tumor malignancy, and poor prognosis in breast cancer patients. Coordinate functions of TET1 and TET3 were needed to activate TNFalpha-p38-MAPK signaling in hypoxia. PMID: 26294212
rs3998860-G allele was significantly associated with the disease severity, suggesting an involvement of TET1 locus in the modulation of apoptosis and liver injury in Nonalcoholic Fatty Liver Disease. PMID: 26356709
Downregulation of TET1 due to hypermethylation is associated with breast cancer metastasis. PMID: 25735355
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相關疾病:
A chromosomal aberration involving TET1 may be a cause of acute leukemias (PubMed:12646957). Translocation t(10;11)(q22;q23) with KMT2A/MLL1. This is a rare chromosomal translocation 5' KMT2A/MLL1-TET1 3' (PubMed:12124344, PubMed:12646957).
亞細胞定位:
Nucleus. Chromosome.
蛋白家族:
TET family
組織特異性:
Expressed in fetal heart, lung and brain, and in adult skeletal muscle, thymus and ovary. Not detected in adult heart, lung or brain. Up-regulated in glioblastoma cells (at protein level).