TET1

DNA methylation is an epigenetic mechanism that is important for controlling gene expression. TET1 is a demethylase that belongs to the TET (ten-eleven translocation) family. Members of the TET protein family function in the DNA methylation process and gene activation.

Full Name

tet oncogene 1

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 (PubMed:19372391, PubMed:21496894).
Also mediates subsequent conversion of 5hmC into 5-formylcytosine (5fC), and conversion of 5fC to 5-carboxylcytosine (5caC) (PubMed:21778364).
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 (PubMed:33833093).
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 (PubMed:31278917).
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 (PubMed:25284789).
Binds preferentially to DNA containing cytidine-phosphate-guanosine (CpG) dinucleotides over CpH (H=A, T, and C), hemimethylated-CpG and hemimethylated-hydroxymethyl-CpG (PubMed:29276034).
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 (PubMed:33833093).

Biological Process

Biological Process 5-methylcytosine catabolic processSource:InterPro
Biological Process chromatin organizationSource:UniProtKB-KW
Biological Process DNA demethylationSource:UniProtKB1 Publication
Biological Process inner cell mass cell differentiationSource:UniProtKB
Biological Process negative regulation of cell migrationSource:ComplexPortal1 Publication
Biological Process negative regulation of DNA methylation-dependent heterochromatin assemblySource:UniProtKB1 Publication
Biological Process negative regulation of stem cell population maintenanceSource:ComplexPortal1 Publication
Biological Process negative regulation of transcription by RNA polymerase IISource:ComplexPortal1 Publication
Biological Process negative regulation of transforming growth factor beta receptor signaling pathwaySource:ComplexPortal1 Publication
Biological Process oxidative demethylationSource:GO_Central1 Publication
Biological Process positive regulation of cell population proliferationSource:UniProtKB1 Publication
Biological Process positive regulation of histone methylationSource:UniProtKB1 Publication
Biological Process positive regulation of stem cell population maintenanceSource:ComplexPortal1 Publication
Biological Process positive regulation of transcription by RNA polymerase IISource:UniProtKB
Biological Process protein O-linked glycosylationSource:UniProtKB
Biological Process stem cell population maintenanceSource:UniProtKB

Cellular Location

Nucleus
Chromosome

Involvement in disease

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).

PTM

Glycosylated. Interaction with OGT leads to GlcNAcylation (By similarity).