Affinage

TET1

Methylcytosine dioxygenase TET1 · UniProt Q8NFU7

Length
2136 aa
Mass
235.3 kDa
Annotated
2026-06-10
100 papers in source corpus 40 papers cited in narrative 40 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TET1 is a 2-oxoglutarate- and Fe(II)-dependent dioxygenase that oxidizes 5-methylcytosine to 5-hydroxymethylcytosine in DNA, initiating active DNA demethylation that shapes pluripotency, lineage specification, and tissue homeostasis (PMID:19372391, PMID:35075236). Its catalytic output feeds the TET1-TDG-base-excision-repair pathway, which sequentially processes symmetrically methylated CpGs to complete demethylation without generating double-strand breaks (PMID:26932196). In embryonic stem cells TET1 binds genome-wide at CpG-rich transcription start sites and gene bodies, where it operates complementarily and competitively with the de novo methyltransferase DNMT3A1 to set methylation boundaries and protect DNA methylation canyons (PMID:21490601, PMID:30001199, PMID:26598602). Beyond catalysis, TET1 acts as a non-enzymatic chromatin scaffold: loss of TET1 — but not loss of its catalytic activity — derepresses bivalent developmental genes by impairing recruitment of PRC2 and the SIN3A/HDAC1 co-repressor machinery and reducing H3K27me3, and this structural function also restrains cell-cycle genes such as p21/Cdkn1a (PMID:29733394, PMID:35150568, PMID:35456045). TET1 is recruited to defined loci through partners including GADD45A acting at R-loops, NONO, PSPC1, FOXA1, FOXA2, ETV2, and ZFP281, directing demethylation and downstream programs in development and differentiation (PMID:30617255, PMID:27257062, PMID:32286661, PMID:35675764, PMID:35798741, PMID:38237590). Two isoforms partition these activities: full-length TET1 bearing the CXXC domain is restricted to early embryos, ESCs, and PGCs, whereas the short isoform TET1s lacking CXXC is targeted to late-replicating heterochromatin via CRL4(VprBP)-mediated ubiquitination and UHRF1 recognition, spreading 5mC oxidation and activating LINE1 (PMID:27916660, PMID:36056023). Through these mechanisms TET1 controls Wnt and Notch signaling in stem cell niches, neurogenesis and myelin repair, metabolic and antioxidant gene expression, and is engineerable as a programmable demethylase via TALE and dCas9 fusions (PMID:27856615, PMID:34731622, PMID:34099715, PMID:24108092, PMID:27571369). TET1 expression is itself regulated by oncogenic KRAS/ERK, HIF-1, NF-κB, and post-transcriptional inputs, positioning it within disease contexts including cancer and leukemia (PMID:25466250, PMID:24835990, PMID:29938218, PMID:32409690).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2009 High

    Established the founding biochemical identity of TET1 by showing it is an enzyme that converts 5mC to 5hmC, defining a new chemical step in DNA modification.

    Evidence In vitro enzymatic assay and RNAi depletion with 5hmC quantification in mouse ESCs

    PMID:19372391

    Open questions at the time
    • Did not resolve downstream fate of 5hmC
    • Genomic targeting and recruitment mechanism unaddressed
  2. 2011 High

    Showed TET1 genomic binding is concentrated at CpG-rich promoters and that it physically associates with the SIN3A co-repressor, the first evidence that TET1 functions in transcriptional repression beyond catalysis.

    Evidence Genome-wide ChIP-seq and co-immunoprecipitation with SIN3A in ESCs

    PMID:21490601

    Open questions at the time
    • Did not separate catalytic from scaffolding contributions
    • Mechanism of SIN3A-directed repression undefined
  3. 2011 High

    Placed TET1 upstream of Nodal/Lefty1 signaling in ESC lineage choice, linking the enzyme to developmental gene regulation.

    Evidence RNAi knockdown, embryoid body differentiation, and mouse chimera assays

    PMID:21295276

    Open questions at the time
    • Direct demethylation target at Lefty1 not yet mapped at this stage
    • Catalytic vs structural requirement unresolved
  4. 2013 High

    Demonstrated TET1 catalytic activity is sufficient for targeted, locus-specific demethylation and gene activation, validating it as a programmable epigenetic effector.

    Evidence TALE-TET1 catalytic-domain fusions with bisulfite sequencing and expression readout in human cells

    PMID:24108092

    Open questions at the time
    • Off-target demethylation not fully quantified
    • Endogenous recruitment determinants not addressed
  5. 2016 High

    Reconstituted the TET1-TDG-BER pathway biochemically, explaining how iterative oxidation couples to base excision to achieve demethylation without double-strand breaks.

    Evidence Biochemical reconstitution, Co-IP, and in vitro enzymatic assays

    PMID:26932196

    Open questions at the time
    • In vivo coordination of strand asymmetry not directly visualized
    • Regulation of TDG handoff in chromatin context unknown
  6. 2016 High

    Distinguished isoform-specific function, showing the CXXC-bearing full-length TET1 is developmentally restricted and required for imprint erasure, while a short somatic isoform exists.

    Evidence Isoform expression analysis, ChIP-seq, bisulfite sequencing, and mouse knockin genetics

    PMID:27916660

    Open questions at the time
    • Targeting mechanism of the short isoform not yet defined here
    • Functional differences in somatic tissues incompletely mapped
  7. 2016 High

    Showed TET1 flanking-sequence preferences and demonstrated dCas9-SunTag-TET1 catalytic targeting works in vivo, advancing both substrate understanding and editing utility.

    Evidence dCas9-SunTag-scFv-TET1 fusion with bisulfite sequencing in cells and mouse fetuses

    PMID:27571369

    Open questions at the time
    • Durability of demethylation over divisions not established
    • Endogenous targeting still distinct from engineered systems
  8. 2019 High

    Identified R-loops and GADD45A as a recruitment route, explaining how TET1 reaches specific CpG island promoters for demethylation.

    Evidence Direct R-loop binding assays, Co-IP, genome-wide TET1 ChIP-seq, and RNase H1 manipulation in ESCs

    PMID:26546041 PMID:30617255

    Open questions at the time
    • Generality across all TET1 sites not established
    • How R-loop dynamics are regulated to time recruitment unclear
  9. 2018 High

    Defined the antagonistic and complementary relationship between TET1 and DNMT3A1 that establishes methylation boundaries and co-regulates PRC2-dependent H3K27me3 at bivalent promoters.

    Evidence ChIP-seq, whole-genome bisulfite sequencing, and transcriptomics in knockout mouse ESCs

    PMID:29733394 PMID:30001199

    Open questions at the time
    • Mechanism of mutual exclusion at canyons not structurally resolved
    • Causal order of methylation and H3K27me3 changes incompletely separated
  10. 2022 High

    Genetically separated catalytic from non-catalytic TET1 function, establishing that scaffolding of PRC2/SIN3A and maintenance of H3K27me3 at bivalent and cell-cycle genes is demethylase-independent.

    Evidence Catalytic-inactive knockin versus knockout ESCs and mice with ChIP-seq, RNA-seq, and bisulfite sequencing

    PMID:35150568 PMID:35456045

    Open questions at the time
    • Structural basis of PRC2/SIN3A bridging undefined
    • How non-catalytic occupancy is targeted independent of catalysis unclear
  11. 2022 High

    Revealed isoform-selective heterochromatin targeting whereby ubiquitinated TET1s is recognized by UHRF1 to oxidize and decondense heterochromatin and activate LINE1.

    Evidence Live-cell imaging, Co-IP, ubiquitination assays, and domain-deletion mutants with 5mC/5hmC profiling

    PMID:36056023

    Open questions at the time
    • Physiological trigger for TET1s heterochromatin spreading unknown
    • Consequences of LINE1 activation in vivo not fully traced
  12. 2022 High

    Extended TET1 recruitment partners to NONO, PSPC1, FOXA2, and FMRP, linking it to neuronal gene control, bivalent promoter maintenance, β-cell differentiation, and m5C RNA demethylation.

    Evidence Co-IP with domain mapping, interactome proteomics, triple-KO hESC differentiation, and in vitro m5C demethylation assays

    PMID:32286661 PMID:35290126 PMID:35675764 PMID:35798741

    Open questions at the time
    • Whether RNA m5C demethylation is a major in vivo TET1 function unresolved
    • Hierarchy among multiple recruitment partners at shared loci unclear
  13. 2023 Medium

    Consolidated tissue-level catalytic roles of TET1 across intestinal Wnt signaling, neural Notch signaling, myelin repair, antioxidant defense, and metabolic gene control through locus-specific demethylation.

    Evidence Lineage- and tissue-specific conditional knockouts with 5hmC profiling, bisulfite sequencing, and physiological injury or differentiation models

    PMID:27856615 PMID:32855402 PMID:34099715 PMID:34731622 PMID:34738906 PMID:37908721

    Open questions at the time
    • Catalytic versus scaffolding contribution varies by tissue and is not uniformly dissected
    • Direct target sets incompletely defined in most tissues
  14. 2024 Medium

    Showed transcription-factor co-occupancy (ZFP281) at R-loop-dependent promoters dynamically reconfigures TET1 binding across pluripotency states.

    Evidence Zfp281 KO and degron models with ChIP-seq co-occupancy and R-loop manipulation

    PMID:38237590

    Open questions at the time
    • Direct physical interaction between ZFP281 and TET1 not established
    • Functional output of redistributed binding on methylation incompletely mapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the relative balance of TET1 catalytic versus scaffolding activity is selected at a given locus, and the structural basis by which TET1 bridges PRC2/SIN3A/HDAC1 repressive complexes, remain open.
  • No structural model of TET1-PRC2/SIN3A scaffolding
  • Unified logic governing catalytic vs non-catalytic mode switching is undefined
  • In vivo significance of RNA m5C demethylation versus DNA demethylation unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016491 oxidoreductase activity 3 GO:0140097 catalytic activity, acting on DNA 3 GO:0140110 transcription regulator activity 3 GO:0003677 DNA binding 2 GO:0140098 catalytic activity, acting on RNA 1
Localization
GO:0000228 nuclear chromosome 3 GO:0005634 nucleus 2
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-1643685 Disease 3 R-HSA-4839726 Chromatin organization 3 R-HSA-74160 Gene expression (Transcription) 3
Partners
DNMT3AEZH2FOXA1GADD45ANONOPSPC1SIN3ATDG
Complex memberships
PRC2SIN3A co-repressor complexTET1-TDG-BER demethylation complex

Evidence

Reading pass · 40 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2009 TET1 is a 2-oxoglutarate (2OG)- and Fe(II)-dependent dioxygenase that catalyzes the conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) in DNA, both in cultured cells and in vitro. RNAi-mediated depletion of TET1 decreases 5hmC levels in mouse embryonic stem cells. In vitro enzymatic assay, RNAi knockdown with 5hmC quantification, computational homology analysis Science High 19372391
2011 TET1 binds throughout the genome of embryonic stem cells, predominantly at CpG-rich transcription start sites and gene bodies. TET1 associates and co-localizes with the SIN3A co-repressor complex, indicating a role in transcriptional repression independent of or in addition to its catalytic activity. ChIP-seq genome-wide binding analysis, co-immunoprecipitation with SIN3A Nature High 21490601
2011 Tet1 and Tet2 are Oct4-regulated enzymes in mouse ESCs. Tet1 depletion diminishes expression of the Nodal antagonist Lefty1, leading to hyperactive Nodal signaling and skewed differentiation into endoderm-mesoderm lineage, placing Tet1 upstream of Nodal/Lefty1 signaling in ESC lineage specification. RNAi knockdown, embryoid body differentiation assay, gene expression analysis, mouse chimera experiments Cell stem cell High 21295276
2013 TALE-TET1 fusion proteins (TALE repeat arrays fused to the TET1 hydroxylase catalytic domain) can achieve targeted demethylation of specific CpG positions in human cells, and modification of methylated promoter CpGs leads to substantial increases in endogenous gene expression. TALE-TET1 fusion protein targeting, bisulfite sequencing, gene expression analysis Nature biotechnology High 24108092
2013 Depleting HMGA2 induces TET1 expression; TET1 then binds and demethylates its own promoter and the promoters of HOXA genes (including HOXA7 and HOXA9), establishing a HMGA2-TET1-HOXA9 pathway that suppresses breast tumor growth and metastasis. RNAi knockdown, ChIP, bisulfite sequencing, mouse xenograft tumor model Proceedings of the National Academy of Sciences of the United States of America Medium 23716660
2016 TET1 and TDG physically interact to oxidize and excise 5mC; biochemical reconstitution demonstrated that the TET1-TDG-BER system is capable of productive DNA demethylation. The mechanism ensures sequential demethylation of symmetrically methylated CpGs, avoiding double-strand break formation. Biochemical reconstitution, co-immunoprecipitation, in vitro enzymatic assay Nature communications High 26932196
2016 The full-length TET1 isoform (TET1e) bearing the CXXC domain is restricted to early embryos, ESCs, and PGCs, while a short isoform (TET1s) lacking the N-terminal CXXC domain is expressed in somatic cells. Global chromatin binding (not targeted CGI binding) correlates with TET1-mediated demethylation; mice expressing only Tet1s fail to erase imprints in PGCs and display developmental defects. Isoform-specific expression analysis, ChIP-seq, bisulfite sequencing, mouse knockin genetics Molecular cell High 27916660
2016 dCas9-SunTag fused to scFv-TET1 catalytic domain achieves targeted DNA demethylation (>50% efficiency at 7/9 loci tested) in cell culture and in vivo in mouse fetuses, causing demethylation-dependent gene upregulation at demethylated regulatory regions. dCas9-SunTag-scFv-TET1 fusion, bisulfite sequencing, gene expression analysis, in vivo mouse experiments Nature biotechnology High 27571369
2015 GADD45a physically interacts with TET1 and functionally cooperates with it in methylcytosine processing. GADD45a requires endogenous TET1 for reporter demethylation, and TET1 hyperinduces 5hmC in the presence of GADD45a while reducing 5fC and 5caC levels, suggesting GADD45a promotes TET1 activity and enhances subsequent oxidized base removal. Co-immunoprecipitation, reporter demethylation assay, 5hmC/5fC/5caC quantification, knockdown experiments Differentiation; research in biological diversity Medium 26546041
2019 GADD45A binds directly to R-loops at CpG island promoters and mediates local DNA demethylation by recruiting TET1. R-loop formation at the TCF21 promoter by lncRNA TARID enables GADD45A binding, which recruits TET1 to drive demethylation. Genomic profiling in ESCs identified thousands of R-loop-dependent TET1 binding sites at CGIs. Direct R-loop binding assays, Co-IP, genome-wide TET1 ChIP-seq, RNase H1 manipulation, 5hmC profiling Nature genetics High 30617255
2018 DNMT3A (specifically DNMT3A1) and TET1 function in a complementary and competitive manner in mouse ESCs: TET1 is enriched at proximal promoters and canyons where DNMT3A1 is excluded, and deletion of Tet1 increases DNMT3A1 binding. TET1 and DNMT3A1 co-regulate PRC2-mediated H3K27me3 enrichment at bivalent promoters. ChIP-seq, whole-genome bisulfite sequencing, knockout mouse ESCs, transcriptome analysis Genome biology High 30001199
2018 Sin3a interacts with Tet1 (via residues Phe147 and Phe182 in the PAH1 domain of Sin3a) to function as a transcriptional coactivator of Lefty1 by demethylating its promoter. Sin3a-Tet1 co-occupancy facilitates transcription of a set of co-target genes in mouse ESCs. Co-immunoprecipitation, site-directed mutagenesis of Sin3a, ChIP-seq, MeDIP-seq, luciferase reporter assay Nucleic acids research High 29733394
2022 Tet1 regulates H3K27 modification and ESC biology through a non-catalytic mechanism: loss of Tet1 (but not loss of catalytic activity) causes aberrant upregulation of bivalent developmental genes, impaired enrichment of PRC2 and Sin3a at bivalent promoters, reduced H3K27me3 and deacetylation, without changes in DNA methylation. Tet1 physically occupies genomic loci overlapping with PRC2 and Sin3a. Catalytic-inactive knockin vs. knockout ESCs and mice, ChIP-seq, RNA-seq, bisulfite sequencing Nucleic acids research High 35150568
2022 FMRP promotes transcription-coupled homologous recombination by interacting with both the m5C writer TRDMT1 and the m5C eraser TET1. FMRP displays higher affinity for DNA:RNA hybrids containing m5C-modified RNA and facilitates demethylation of m5C RNA by TET1 in vitro, acting as a coordinator between writer and eraser. Co-immunoprecipitation, in vitro m5C demethylation assay, domain deletion mutants, DNA repair assays Proceedings of the National Academy of Sciences of the United States of America High 35290126
2014 Oncogenic KRAS suppresses TET1 expression via the ERK signaling pathway, reducing TET1 chromatin occupancy at tumor suppressor gene (TSG) promoters and increasing DNA methylation. KRAS/TET1 double knockdown bypasses KRAS dependence, establishing TET1 suppression as required for KRAS-mediated cellular transformation. RNAi knockdown, ERK pathway inhibition, ChIP, bisulfite sequencing, colony formation assay Cell reports Medium 25466250
2016 FOXA1 physically interacts with TET1 through TET1's CXXC domain, and FOXA1 binding induces TET1 expression via direct binding to its cis-regulatory elements. TET1 co-occupies FOXA1-dependent enhancers and mediates local DNA demethylation and H3K4 methylation in a feed-forward loop. Co-immunoprecipitation, ChIP-seq, bisulfite sequencing, siRNA knockdown Nucleic acids research Medium 27257062
2018 ETV2 directly interacts with TET1 and TET2 (demonstrated by immunoprecipitation); adenoviral expression of ETV2-TET1/TET2 complexes demethylated the Robo4 promoter and induced Robo4 expression in non-endothelial cells, establishing that ETV2-TET1/TET2 complexes drive endothelial cell-specific gene expression through promoter demethylation. Co-immunoprecipitation, adenoviral overexpression, bisulfite sequencing, gene expression analysis Scientific reports Medium 29618782
2015 DAZL, an RNA-binding protein, associates with Tet1 mRNA and enhances its translation. DAZL overexpression in ESCs elevates TET1 protein levels and increases global 5hmC; Dazl null mutation severely stunts 2i-mediated TET1 induction and hydroxymethylation, placing DAZL as a post-transcriptional regulator of TET1. RNA immunoprecipitation (RIP), polysome profiling, Dazl null mutation, 5hmC quantification EMBO reports Medium 26077710
2020 NONO directly interacts with TET1 via its DNA binding domain and recruits TET1 to genomic loci to regulate 5hmC levels. Nono deletion causes significant dissociation of TET1 from chromatin and dysregulation of DNA hydroxymethylation at neuronal genes, impairing neuronal differentiation of mESCs. Co-immunoprecipitation with domain mapping, ChIP-seq, 5hmC profiling, Nono KO rescue experiments Nucleic acids research Medium 32286661
2022 Using a proteomics approach, PSPC1 was identified as a TET1 interactor in ESCs. TET1 and PSPC1 co-occupy bivalent gene promoters overlapping with PRC2; TET1-PSPC1 maintain PRC2 chromatin occupancy at bivalent promoters during ESC-to-EpiLC transition, while lncRNA Neat1 activates bivalent genes by promoting PRC2 binding to mRNAs. TET1 interactome proteomics, ChIP-seq, genome-wide location analysis, PSPC1 knockdown Cell reports Medium 35675764
2020 TET1 acts as an autonomous repressor of thermogenic genes (Ucp1, Ppargc1a) in beige adipocytes through a mechanism that is largely DNA demethylase-independent; instead, TET1 coordinates with HDAC1 to mediate epigenetic repression. Adipose-selective Tet1 knockout improves cold tolerance and protects against diet-induced obesity. Adipose-specific Tet1 KO (Fabp4-Cre), Co-IP with HDAC1, gene expression analysis, thermogenic phenotyping Nature communications Medium 32855402
2021 TET1 physically interacts with SIRT1 via its C-terminal domain and activates SIRT1 deacetylase activity, regulating acetylation-dependent cellular translocation of transcription factors PGC-1α and FOXO1, thereby activating hepatic gluconeogenic gene expression. The AMPK-TET1-SIRT1 axis mediates fasting-induced gluconeogenesis. Co-immunoprecipitation, domain mapping, deacetylase activity assay, Tet1 heterozygous mouse liver analysis eLife Medium 34738906
2022 The Tet1 short isoform (Tet1s) but not full-length Tet1 is recruited to late-replicating heterochromatin via ubiquitination by CRL4(VprBP) and subsequent recognition by Uhrf1. The CXXC zinc finger domain of full-length Tet1 prevents heterochromatin targeting. This isoform-specific targeting leads to spreading of 5mC oxidation to heterochromatin, LINE1 activation, and chromatin decondensation. Live-cell imaging during DNA replication, Co-IP, ubiquitination assay, domain deletion mutants, 5mC/5hmC profiling Nature communications High 36056023
2022 TET1 dioxygenase is required for FOXA2-associated chromatin remodeling in pancreatic β-cell differentiation. TET1 and FOXA2 physically interact in endodermal lineage intermediates; full-length TET1 (but not TET1 catalytic domain alone) rescues β-cell differentiation in TET-deficient hESCs. Co-immunoprecipitation, TET1/2/3 triple knockout hESCs, whole-genome methylation profiling, FOXA2 ChIP-seq, differentiation assays Nature communications High 35798741
2016 Tet1-mediated DNA hydroxymethylation in intestinal stem cells (ISCs) is required for Wnt signaling. Tet1-deficient mice display reduced numbers of proliferative intestinal cells, reduced organoid-forming capacity, and decreased expression of Wnt target genes (Axin2, Lgr5) correlating with lower 5hmC levels at their promoters. Tet1 KO mouse, genome-wide 5hmC mapping (hMeDIP-seq), quantitative gene expression, organoid assay Genes & development High 27856615
2014 Hypoxia transcriptionally activates TET1 in a HIF-1-dependent manner, leading to increased global 5hmC levels and accumulation of 5hmC at hypoxia response element-containing loci, facilitating DNA demethylation and HIF binding. Full induction of hypoxia-responsive genes requires TET1. TET1 knockdown, 5hmC genome-wide mapping, HIF-1 inhibition, gene expression analysis under hypoxia Cell reports Medium 24835990
2018 NF-κB p65 directly binds the TET1 promoter to repress TET1 transcription in breast cancer cells, establishing immune signaling as an upstream regulator of TET1 expression and 5hmC levels. ChIP showing p65 binding to TET1 promoter, NF-κB activation/inhibition experiments, in vitro and in vivo mouse studies Science advances Medium 29938218
2020 PARP1 interacts with TET1 protein, and PARP enzymes establish H3K4me3 marks at the TET1 promoter. PARP inhibitor Olaparib abrogates TET1 expression, induces loss of 5hmC marks, and antagonizes leukemic T-ALL growth. TET1 promotes T-ALL growth through its catalytic activity maintaining global 5hmC. Co-immunoprecipitation of PARP1-TET1, ChIP for H3K4me3 at TET1 promoter, TET1 KO mouse, Olaparib treatment in vivo Leukemia Medium 32409690
2016 Hypermethylation of DNA methylation canyons is a key genomic consequence of Tet1/Tet2 double knockout; canyon hypermethylation coincides with disturbed regulation of associated genes, suggesting Tet-dependent demethylation maintains canyon boundaries and prevents invasive methylation. Whole-genome bisulfite sequencing, RNA-seq in Tet1/Tet2 DKO mouse embryonic fibroblasts Molecular and cellular biology Medium 26598602
2022 TET1 and TET2 exhibit pronounced flanking sequence effects on catalytic activity (20-fold for TET1, 70-fold for TET2). TET1 and TET2 show similar flanking sequence preferences for both 5mC and 5hmC substrates. These preferences are reflected in genome-wide patterns of 5hmC and DNA demethylation in human and mouse cells. In vitro enzymatic assay with randomized flanking sequence libraries, single-molecule readout Communications biology High 35075236
2021 Tet1 is required for adult myelin repair; constitutive and inducible oligodendrocyte-specific ablation of Tet1 (but not Tet2) recapitulates age-related decline in remyelination. TET1 targets include Slc gene family members (notably SLC12A2), whose expression is higher in Tet1-overexpressing cells and lower in old or Tet1-KO mice. Oligodendrocyte-specific conditional KO, 5hmC profiling, transcriptomics, demyelination lesion model, zebrafish slc12a2b mutants Nature communications High 34099715
2020 DSCR1 binds to TET1 introns to regulate splicing of TET1, modulating TET1 protein levels. TET1 in turn controls demethylation of the miR-124 promoter to modulate miR-124 expression in adult hippocampal neurogenesis. Correcting TET1 levels in DSCR1 KO mice is sufficient to prevent defective neurogenesis. DSCR1 KO mouse, RNA splicing analysis, TET1 level correction, 5hmC profiling at miR-124 promoter, adult neurogenesis assays The EMBO journal Medium 31304631
2016 ERK/c-Jun signaling recruits Tet1 to the EBV Zta promoter; c-Jun interacts with Tet1 (shown by Co-IP) and facilitates Tet1 binding to Zta, leading to promoter demethylation, Zta expression, and EBV reactivation. Tet1 knockdown attenuates TPA-induced Zta demethylation and EBV reactivation. Co-immunoprecipitation of c-Jun and Tet1, ChIP, bisulfite sequencing, siRNA knockdown Scientific reports Medium 27708396
2019 TET1 recruits co-repressor proteins SIN3A and the histone lysine methyltransferase EZH2 to osteogenic genes in human mesenchymal stem cells, acting as a repressor of both osteogenesis and adipogenesis. siRNA knockdown, Co-IP of TET1 with SIN3A and EZH2, ChIP, differentiation assays Epigenetics & chromatin Medium 30606231
2021 Tet1 promotes demethylation of the Dll3 and Notch1 promoters in hippocampal neural stem cells; Tet1 downregulation in FGR causes hypermethylation of these promoters and inhibition of Notch signaling, reducing NSC proliferation. Tet1 overexpression activates Notch signaling and rescues neurogenesis deficits. Tet1 KO/overexpression in FGR mouse model, bisulfite sequencing, Notch signaling assays, neurogenesis quantification Cell reports Medium 34731622
2022 Tet1 loss (but not catalytic inactivation) in ESCs leads to upregulation of p21/Cdkn1a through loss of Tet1-dependent PRC2 (Ezh2) and H3K27me3 enrichment at the p21 promoter, causing delayed G1 cell cycle progression. Tet1 directly occupies the p21 promoter overlapping with H3K27me3. Tet1 KO vs. catalytic-mutant mESCs, ChIP for Ezh2 and H3K27me3 at p21 promoter, p21 knockdown rescue, cell cycle analysis Cells Medium 35456045
2021 Tet1 is essential for deposition of 5hmC and facultative histone marks H3K27me3 and H2AK119ub at pericentromeric heterochromatin (PCH), and recruits RING1B (PRC1 component) to PCH. This TET1-dependent mechanism underlies chromocenter clustering in DNA hypomethylated cells via liquid-liquid phase separation. Tet1 KO ESCs, 5hmC ChIP-seq at PCH, H3K27me3 and H2AK119ub ChIP, RING1B co-localization, phase separation assays PLoS genetics Medium 34166371
2023 Tet1 reduces 5mC levels in an enzymatic activity-dependent manner at the promoters of Sod1 and Sod2 to promote their expression in kidney, thereby reducing injury-induced excessive ROS and acute kidney injury. Tet1 KO mice, bisulfite sequencing of Sod1/Sod2 promoters, ChIP, ROS quantification, I/R and UUO injury models Theranostics Medium 37908721
2020 Morphine and naloxone directly bind to TET1 protein via three key residues (1880-1882) and inhibit its DNA demethylation activity while facilitating neural stem cell proliferation through a receptor-independent, TET1-dependent pathway. Molecular docking, direct binding assay, TET1 demethylation activity assay with opioids, TET1 knockdown, NSC proliferation assay Cell reports Medium 32187535
2024 ZFP281 and TET1 co-occupy gene promoters in a manner dependent on R-loop formation at ZFP281-targeted gene promoters; this co-occupancy undergoes bimodal dynamics during naive-formative-primed pluripotency transitions to regulate DNA methylation and gene expression. Zfp281 KO and degron knockin cell models, ChIP-seq co-occupancy analysis, R-loop manipulation Developmental cell Medium 38237590

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science (New York, N.Y.) 4469 19372391
2011 TET1 and hydroxymethylcytosine in transcription and DNA methylation fidelity. Nature 819 21490601
2011 Tet1 and Tet2 regulate 5-hydroxymethylcytosine production and cell lineage specification in mouse embryonic stem cells. Cell stem cell 635 21295276
2016 Targeted DNA demethylation in vivo using dCas9-peptide repeat and scFv-TET1 catalytic domain fusions. Nature biotechnology 391 27571369
2013 Targeted DNA demethylation and activation of endogenous genes using programmable TALE-TET1 fusion proteins. Nature biotechnology 369 24108092
2013 HMGA2/TET1/HOXA9 signaling pathway regulates breast cancer growth and metastasis. Proceedings of the National Academy of Sciences of the United States of America 230 23716660
2019 GADD45A binds R-loops and recruits TET1 to CpG island promoters. Nature genetics 225 30617255
2015 TET1 is a tumor suppressor of hematopoietic malignancy. Nature immunology 189 25867473
2016 Biochemical reconstitution of TET1-TDG-BER-dependent active DNA demethylation reveals a highly coordinated mechanism. Nature communications 176 26932196
2014 TET1-mediated hydroxymethylation facilitates hypoxic gene induction in neuroblastoma. Cell reports 143 24835990
2015 Role of Tet1 and 5-hydroxymethylcytosine in cocaine action. Nature neuroscience 132 25774451
2022 FMRP promotes transcription-coupled homologous recombination via facilitating TET1-mediated m5C RNA modification demethylation. Proceedings of the National Academy of Sciences of the United States of America 129 35290126
2018 DNMT3A and TET1 cooperate to regulate promoter epigenetic landscapes in mouse embryonic stem cells. Genome biology 124 30001199
2018 TET1-Mediated Hypomethylation Activates Oncogenic Signaling in Triple-Negative Breast Cancer. Cancer research 119 29891505
2018 Tet1 and Tet2 maintain mesenchymal stem cell homeostasis via demethylation of the P2rX7 promoter. Nature communications 99 29858571
2015 Combined Loss of Tet1 and Tet2 Promotes B Cell, but Not Myeloid Malignancies, in Mice. Cell reports 90 26586431
2016 Isoform Switch of TET1 Regulates DNA Demethylation and Mouse Development. Molecular cell 86 27916660
2018 Immunity drives TET1 regulation in cancer through NF-κB. Science advances 70 29938218
2015 Tet1-mediated DNA demethylation regulates neuronal cell death induced by oxidative stress. Scientific reports 69 25561289
2019 Specific functions of TET1 and TET2 in regulating mesenchymal cell lineage determination. Epigenetics & chromatin 68 30606231
2019 TET1-mediated DNA hydroxymethylation activates inhibitors of the Wnt/β-catenin signaling pathway to suppress EMT in pancreatic tumor cells. Journal of experimental & clinical cancer research : CR 65 31399111
2014 Suppression of TET1-dependent DNA demethylation is essential for KRAS-mediated transformation. Cell reports 62 25466250
2021 TET1-mediated DNA hydroxymethylation regulates adult remyelination in mice. Nature communications 57 34099715
2020 TET1 is a beige adipocyte-selective epigenetic suppressor of thermogenesis. Nature communications 55 32855402
2016 FOXA1 potentiates lineage-specific enhancer activation through modulating TET1 expression and function. Nucleic acids research 55 27257062
2016 Epigenetic regulation of intestinal stem cells by Tet1-mediated DNA hydroxymethylation. Genes & development 54 27856615
2018 Sin3a-Tet1 interaction activates gene transcription and is required for embryonic stem cell pluripotency. Nucleic acids research 52 29733394
2017 Tet1 in Nucleus Accumbens Opposes Depression- and Anxiety-Like Behaviors. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 52 28074830
2022 The DNA dioxygenase Tet1 regulates H3K27 modification and embryonic stem cell biology independent of its catalytic activity. Nucleic acids research 51 35150568
2015 Tet1 and Tet2 Protect DNA Methylation Canyons against Hypermethylation. Molecular and cellular biology 51 26598602
2023 hsa_circ_0007919 induces LIG1 transcription by binding to FOXA1/TET1 to enhance the DNA damage response and promote gemcitabine resistance in pancreatic ductal adenocarcinoma. Molecular cancer 49 38044421
2021 Advances in the DNA methylation hydroxylase TET1. Biomarker research 49 34656178
2019 p53-Suppressed Oncogene TET1 Prevents Cellular Aging in Lung Cancer. Cancer research 49 30622117
2021 Circular RNA 0025984 Ameliorates Ischemic Stroke Injury and Protects Astrocytes Through miR-143-3p/TET1/ORP150 Pathway. Molecular neurobiology 47 34435328
2018 Pluripotency transcription factors and Tet1/2 maintain Brd4-independent stem cell identity. Nature cell biology 45 29662175
2017 Methamphetamine Induces TET1- and TET3-Dependent DNA Hydroxymethylation of Crh and Avp Genes in the Rat Nucleus Accumbens. Molecular neurobiology 41 28842817
2015 GADD45a physically and functionally interacts with TET1. Differentiation; research in biological diversity 41 26546041
2021 Tet1 Deficiency Leads to Premature Ovarian Failure. Frontiers in cell and developmental biology 39 33834024
2019 TET1 promotes 5hmC-dependent stemness, and inhibits a 5hmC-independent epithelial-mesenchymal transition, in cervical precancerous lesions. Cancer letters 39 30771438
2022 Upregulation of CRABP2 by TET1-mediated DNA hydroxymethylation attenuates mitochondrial apoptosis and promotes oxaliplatin resistance in gastric cancer. Cell death & disease 36 36195596
2020 MSTN Mutant Promotes Myogenic Differentiation by Increasing Demethylase TET1 Expression via the SMAD2/SMAD3 Pathway. International journal of biological sciences 36 32210722
2020 Role of TET1 and 5hmC in an Obesity-Linked Pathway Driving Cancer Stem Cells in Triple-Negative Breast Cancer. Molecular cancer research : MCR 33 32913111
2019 Inhibition of Tet1- and Tet2-mediated DNA demethylation promotes immunomodulation of periodontal ligament stem cells. Cell death & disease 33 31611558
2020 H19/TET1 axis promotes TGF-β signaling linked to endothelial-to-mesenchymal transition. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 32 32374060
2017 Hypoxia-induced TET1 facilitates trophoblast cell migration and invasion through HIF1α signaling pathway. Scientific reports 32 28808304
2021 Fetal growth restriction impairs hippocampal neurogenesis and cognition via Tet1 in offspring. Cell reports 31 34731622
2020 TET1 promotes growth of T-cell acute lymphoblastic leukemia and can be antagonized via PARP inhibition. Leukemia 31 32409690
2023 Saikosaponin a activates tet1/dll3/notch1 signalling and promotes hippocampal neurogenesis to improve depression-like behavior in mice. Journal of ethnopharmacology 30 37844745
2019 TET1 reprograms the epithelial ovarian cancer epigenome and reveals casein kinase 2α as a therapeutic target. The Journal of pathology 30 30883733
2023 Tet1 deficiency exacerbates oxidative stress in acute kidney injury by regulating superoxide dismutase. Theranostics 29 37908721
2021 The hepatic AMPK-TET1-SIRT1 axis regulates glucose homeostasis. eLife 29 34738906
2020 HIF1α/TET1 Pathway Mediates Hypoxia-Induced Adipocytokine Promoter Hypomethylation in Human Adipocytes. Cells 28 31935962
2024 CRISPR/dCas9-Tet1-Mediated DNA Methylation Editing. Bio-protocol 27 38686348
2023 TET1 and TDG Suppress Inflammatory Response in Intestinal Tumorigenesis: Implications for Colorectal Tumors With the CpG Island Methylator Phenotype. Gastroenterology 26 36764492
2018 ETV2-TET1/TET2 Complexes Induce Endothelial Cell-Specific Robo4 Expression via Promoter Demethylation. Scientific reports 26 29618782
2016 miR-29 regulates Tet1 expression and contributes to early differentiation of mouse ESCs. Oncotarget 26 27449105
2016 Association of TET1 expression with colorectal cancer progression. Scandinavian journal of gastroenterology 26 27846738
2021 TET1 upregulation drives cancer cell growth through aberrant enhancer hydroxymethylation of HMGA2 in hepatocellular carcinoma. Cancer science 24 33970549
2020 Nono deficiency compromises TET1 chromatin association and impedes neuronal differentiation of mouse embryonic stem cells. Nucleic acids research 24 32286661
2023 Role of TET1-mediated epigenetic modulation in Alzheimer's disease. Neurobiology of disease 23 37562656
2022 Flanking sequences influence the activity of TET1 and TET2 methylcytosine dioxygenases and affect genomic 5hmC patterns. Communications biology 23 35075236
2022 TET1 dioxygenase is required for FOXA2-associated chromatin remodeling in pancreatic beta-cell differentiation. Nature communications 22 35798741
2022 Interactive regulation of DNA demethylase gene TET1 and m6A methyltransferase gene METTL3 in myoblast differentiation. International journal of biological macromolecules 22 36375665
2019 Label-Free Raman Observation of TET1 Protein-Mediated Epigenetic Alterations in DNA. Analytical chemistry 22 31074614
2017 TET1 deficiency attenuates the DNA damage response and promotes resistance to DNA damaging agents. Epigenetics 22 28758831
2016 TET1-GPER-PI3K/AKT pathway is involved in insulin-driven endometrial cancer cell proliferation. Biochemical and biophysical research communications 22 27889612
2024 Microbiota regulates the TET1-mediated DNA hydroxymethylation program in innate lymphoid cell differentiation. Nature communications 21 38839760
2022 A TET1-PSPC1-Neat1 molecular axis modulates PRC2 functions in controlling stem cell bivalency. Cell reports 21 35675764
2020 TET1 and 5-Hydroxymethylation Preserve the Stem Cell State of Mouse Trophoblast. Stem cell reports 21 32442533
2018 Ten-eleven translocation 1 (TET1) gene is a potential target of miR-21-5p in human colorectal cancer. Surgical oncology 21 29549908
2015 DAZL regulates Tet1 translation in murine embryonic stem cells. EMBO reports 21 26077710
2023 Hypoxia switches TET1 from being tumor-suppressive to oncogenic. Oncogene 20 37020036
2020 MicroRNA-191 regulates endometrial cancer cell growth via TET1-mediated epigenetic modulation of APC. Journal of biochemistry 20 32003827
2021 TET1 promotes RXRα expression and adipogenesis through DNA demethylation. Biochimica et biophysica acta. Molecular and cell biology of lipids 19 33684567
2020 TET1 downregulates epithelial-mesenchymal transition and chemoresistance in PDAC by demethylating CHL1 to inhibit the Hedgehog signaling pathway. Oncogene 19 32753651
2019 DSCR1-mediated TET1 splicing regulates miR-124 expression to control adult hippocampal neurogenesis. The EMBO journal 19 31304631
2023 DNA methylation patterns suggest the involvement of DNMT3B and TET1 in osteosarcoma development. Molecular genetics and genomics : MGG 18 37020053
2019 TET1 suppresses colon cancer proliferation by impairing β-catenin signal pathway. Journal of cellular biochemistry 18 30825236
2018 Editing of DNA Methylation Using dCas9-Peptide Repeat and scFv-TET1 Catalytic Domain Fusions. Methods in molecular biology (Clifton, N.J.) 17 29524149
2020 TET1 is a Tumor Suppressor That Inhibits Papillary Thyroid Carcinoma Cell Migration and Invasion. International journal of endocrinology 16 32089682
2020 Distinct and stage-specific contributions of TET1 and TET2 to stepwise cytosine oxidation in the transition from naive to primed pluripotency. Scientific reports 16 32694513
2017 Dynamic expression of TET1, TET2, and TET3 dioxygenases in mouse and human placentas throughout gestation. Placenta 16 29108636
2020 Morphine and Naloxone Facilitate Neural Stem Cells Proliferation via a TET1-Dependent and Receptor-Independent Pathway. Cell reports 15 32187535
2019 Endogenous epitope-tagging of Tet1, Tet2 and Tet3 identifies TET2 as a naïve pluripotency marker. Life science alliance 15 31582397
2022 Tet1 Suppresses p21 to Ensure Proper Cell Cycle Progression in Embryonic Stem Cells. Cells 14 35456045
2022 Isoform-specific and ubiquitination dependent recruitment of Tet1 to replicating heterochromatin modulates methylcytosine oxidation. Nature communications 14 36056023
2019 Hydroxyurea promotes TET1 expression and induces apoptosis in osteosarcoma cells. Bioscience reports 14 30988069
2017 TET1 inhibits cell proliferation by inducing RASSF5 expression. Oncotarget 14 29156803
2024 ZFP281 controls transcriptional and epigenetic changes promoting mouse pluripotent state transitions via DNMT3 and TET1. Developmental cell 13 38237590
2024 Epigenetic regulation of DNA repair gene program by Hippo/YAP1-TET1 axis mediates sorafenib resistance in HCC. Cellular and molecular life sciences : CMLS 13 38967794
2022 Competitive binding of TET1 and DNMT3A/B cooperates the DNA methylation pattern in human embryonic stem cells. Biochimica et biophysica acta. Gene regulatory mechanisms 13 35998875
2020 Coordination of germ layer lineage choice by TET1 during primed pluripotency. Genes & development 13 32115407
2017 TET1-mediated DNA hypomethylation regulates the expression of MUC4 in lung cancer. Genes & cancer 13 28680536
2016 ERK/c-Jun Recruits Tet1 to Induce Zta Expression and Epstein-Barr Virus Reactivation through DNA Demethylation. Scientific reports 13 27708396
2004 Performance attributes of the LCx HCV RNA quantitative assay. Journal of virological methods 13 14667537
2022 Non-psychotropic cannabinoids as inhibitors of TET1 protein. Bioorganic chemistry 12 35462234
2023 TET1-TRPV4 Signaling Contributes to Bone Cancer Pain in Rats. Brain sciences 11 37190609
2023 TET1 Regulates Skeletal Stem-Cell Mediated Cartilage Regeneration. Arthritis & rheumatology (Hoboken, N.J.) 11 37610277
2022 TET1-induced DNA demethylation in dentate gyrus is important for reward conditioning and reinforcement. Molecular neurobiology 11 35705787
2021 Tet1 regulates epigenetic remodeling of the pericentromeric heterochromatin and chromocenter organization in DNA hypomethylated cells. PLoS genetics 11 34166371

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