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FLASH GENE
Symbol TET1 contributors: mct/ - updated : 09-03-2021
HGNC name tet oncogene 1
HGNC id 29484
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a zinc-binding CXXC domain (which MLL also contains) within a methyltransferase domain, a domain known to bind to unmethylated CpG sites, which are present abundantly in CpG islands
  • three nuclear localizations signals
  • an alpha-helical coiled-coil region
    • HOMOLOGY
    interspecies ortholog to murine Cxxc6
    Homologene
    FAMILY
  • TET family
    • CATEGORY regulatory , DNA associated
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus
    basic FUNCTION
  • having zinc ion binding, DNA binding activities
  • could catalyse the conversion of 5-methylcytosine (5mC) of DNA to 5-hydroxymethylcytosine (5hmC), raising the possibility that DNA demethylation may be a TET1-mediated process
  • role for TET1 in regulating DNA methylation status
  • seems to have a role in maintaining ES cell fate, which is consistent with its role in ICM (inner cell mass) cell specification
  • potential TET1-induced oxidation-deamination mechanism for active DNA demethylation in mammals
  • critical factor to initiate an oxidation-deamination mechanism underlying active DNA demethylation in mammals
  • required for neuronal activity-induced, region-specific, active DNA demethylation and gene expression in the adult brain
  • dual biological role of TET1, one in which it removes aberrant DNA methylation and another that ensures the timely DNA methylation and silencing of target genes during differentiation
  • has a role in transcriptional repression
  • having an important function in the regulation of DNA methylation fidelity
  • function for TET1 in meiosis and meiotic gene activation in female germ cells
  • specific function of TET1 in germ cell development
  • is required for binding of OGT to chromatin affecting TET1 activity
  • TET1 is required for cell proliferation and that this process is mediated through the RB1 pathway
  • TET1, TET2, TET3 influence the balance between neuroectodermal and mesodermal fate choice by inhibiting Wnt signaling
  • TET1 promotes RASSF5 expression by demethylating a CpG site within RASSF5 promoter
  • TET1 and TET2 play a critical role in maintaining bone marrow MSCs and bone homeostasis through demethylation of P2RX7 to control exosome and miRNA release
  • TET1 is a repressor of both osteogenesis and adipogenesis, and was found to recruit the co-repressor proteins, SIN3A and the histone lysine methyltransferase, EZH2 to osteogenic genes
  • TET1 maintains spermatogonia stem cells with age, revealing an important role of TET1 in regulating stem cell aging
  • suppressive role of TET1 in the thermogenic gene regulation of beige adipocytes is largely DNA demethylase-independent
  • is a potent beige-selective epigenetic breaker of the thermogenic gene program
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • CXXC5 forms a complex with NANOG, POU5F1, TET1, and TET2 and facilitates their proper recruitment to regulatory regions of pluripotency and TET genes in ESCs to positively regulate their transcription
  • TET1-RNF217-SLC40A1 axis regulates likely iron homeostasis
    • INTERACTION
    DNA DNA binding
    RNA
    small molecule metal binding,
  • Zn2+
    • protein
  • NANOG is a direct TET1 target and TET1 regulates NANOG expression by preventing the Nanog promoter from hypermethylation
  • interacts with the SIN3A complex and the extensive colocalization of TET1 and the SIN3A co-repressor complex at target genes suggests that SIN3A has an important function in TET1-mediated gene repression
  • function for TET1 in meiosis and meiotic gene activation in female germ cells (
  • link between TETT activities in regulating CpG island methylation
  • is required for RB1 phosphorylation during G1/S phase transition
  • PRDM14 maintains pluripotency of embryonic stem cells through TET1, TET2-mediated active DNA demethylation
  • ZFP281 interacts with TET1, but not TET2
  • RASSF5, is the key downstream target of TET1
  • GADD45A binds directly to R-loops and mediates local DNA demethylation by recruiting TET1
  • GADD45A binding to R-loops promotes TET1 recruitment and DNA demethylation at CpG island promoters
  • CXXC5 binds to the chromatin and is enriched at promoters and enhancers of TET1, TET2, and pluripotency genes
  • TET1 interacts with the pluripotency transcription factor NANOG which may contribute to its biological activity in pluripotent cells
  • TET1 binds to CpG dinucleotides in promoters using its CXXC domain, TET1 also binds to enhancers, though the mechanism involved is unknown
  • RNF217 gene is a target of TET1, mediating the ubiquitination and subsequent degradation of SLC40A1
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral fusion      
    to MLL in acute myeloid leukemia with trilineage dysplasia in t(10;11)(q22;q23)
    constitutional       loss of function
    would promote the stochastic hypermethylation of promoters leading to deregulation of transcription and differentiation
    constitutional     --low  
    depletion of TET1 leads to down-regulation of meiotic genes, which causes defective meiotic prophase including accumulation of non-repaired DSBs, and formation of univalent chromosomes
    Susceptibility to late-onset Alzheimer's disease
    Variant & Polymorphism SNP increasing the risk of late-onset Alzheimer's disease
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    immunologyinflammatory 
    TET1 enzyme could be a promising therapeutic target to inhibit the persistent inflammation caused by macrophages in chronic inflammatory diseases
    ANIMAL & CELL MODELS