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Scientific Background: TET1 Protein or tet methylcytosine dioxygenase 1 is the original member of a family of methylcytosine dioxygenases that perform several steps required for cytosine demethylation and gene activation (1). TET proteins have potential roles in epigenetic regulation through modification of 5mC to hmC. TET1 plays a main role in modulating DNA methylation levels at CpG-rich promoters and also helps in promoting transcription of pluripotency factors as well as participating in the repression of Polycomb-targeted developmental regulators (2).
2. Wu, H. et.al: Dual functions of Tet1 in transcriptional regulation in mouse embryonic stem cells. Nature 473: 389-393, 2011.
NCBI and Uniprot Product Information
Uniprot Description
Function: 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). Conversion of 5mC into 5hmC, 5fC and 5caC probably constitutes the first step in cytosine demethylation. Methylation at the C5 position of cytosine bases is an epigenetic modification of the mammalian genome which plays an important role in transcriptional regulation. In addition to its role in DNA demethylation, plays a more general role in chromatin regulation. Preferentially binds to CpG-rich sequences at promoters of both transcriptionally active and Polycomb-repressed genes. Involved in the recruitment of the O-GlcNAc transferase OGT to CpG-rich transcription start sites of active genes, thereby promoting histone H2B GlcNAcylation by OGT. Also involved in transcription repression of a subset of genes through recruitment of transcriptional repressors to promoters. 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. Ref.1 Ref.7 Ref.8 Ref.9 Ref.11
Catalytic activity: DNA 5-methylcytosine + 2-oxoglutarate + O2 = DNA 5-hydroxymethylcytosine + succinate + CO2. Ref.8 Ref.9DNA 5-hydroxymethylcytosine + 2-oxoglutarate + O2 = DNA 5-formylcytosine + succinate + CO2. Ref.8 Ref.9DNA 5-formylcytosine + 2-oxoglutarate + O2 = DNA 5-carboxylcytosine + succinate + CO2. Ref.8 Ref.9
Cofactor: Binds 1 Fe2+ ion per subunit. Ref.8
Subunit structure: Interacts with HCFC1 and OGT
By similarity. Interacts with SIN3A; recruits the transcriptional corepressor SIN3A to gene promoters. Ref.10
Subcellular location: Nucleus
Probable.
Tissue specificity: Expressed in fetal heart, lung and brain, and in adult skeletal muscle, thymus and ovary. Not detected in adult heart, lung or brain. Ref.1 Ref.6
Post-translational modification: Glycosylated. Interaction with OGT leads to GlcNAcylation
By similarity.
Involvement in disease: A chromosomal aberration involving TET1 may be a cause of acute leukemias. Translocation t(10;11)(q22;q23) with KMT2A/MLL1. This is a rare chromosomal translocation 5' KMT2A/MLL1-TET1 3'.
Sequence similarities: Belongs to the TET family.Contains 1 CXXC-type zinc finger.
Caution: Subsequent steps in cytosine demethylation are subject to discussion. According to a first model cytosine demethylation occurs through deamination of 5hmC into 5-hydroxymethyluracil (5hmU) and subsequent replacement by unmethylated cytosine by the base excision repair system (Ref.9). According to another model, cytosine demethylation is rather mediated via conversion of 5hmC into 5fC and 5caC, followed by excision by TDG and replacement by unmethylated cytosine.
Sequence caution: The sequence CAD28467.3 differs from that shown. Reason: Contaminating sequence. Potential poly-A sequence.
Research Articles on TET1
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Product Notes
The TET1 tet1 (Catalog #AAA515125) is a Recombinant Protein produced from Sf9 insect cells and is intended for research purposes only. The product is available for immediate purchase. The tag for this protein is GST tag!!Expression System||Sf9 insect cells using baculovirus!!Source Note||Recombinant human TET1 (1598-end) was expressed by baculovirus in Sf9 insect cells. AAA Biotech's TET1 can be used in a range of immunoassay formats including, but not limited to, Western Blot (WB). Researchers should empirically determine the suitability of the TET1 tet1 for an application not listed in the data sheet. Researchers commonly develop new applications and it is an integral, important part of the investigative research process. It is sometimes possible for the material contained within the vial of "TET1, Recombinant Protein" to become dispersed throughout the inside of the vial, particularly around the seal of said vial, during shipment and storage. We always suggest centrifuging these vials to consolidate all of the liquid away from the lid and to the bottom of the vial prior to opening. Please be advised that certain products may require dry ice for shipping and that, if this is the case, an additional dry ice fee may also be required.Precautions
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