Cart
Products
<< Back to Epigenetics on Target Home Page
TETs in Epigenetics and Disease
The TET pathway is a central DNA demethylation pathway that regulates gene expression, cell differentiation, stem cell maintenance, and genome stability. The core TET enzymes (TET1, TET2, and TET3) oxidize 5-methylcytosine (5mC) to generate intermediates that ultimately lead to DNA demethylation. Their activity depends on several cofactors and interacting proteins that influence recruitment, enzymatic activity, and chromatin targeting.
| Protein / Family | Epigenetic Function | Disease Association | Key Publications | Key Products |
|---|---|---|---|---|
| CXXC4 (IDAX) | Controls TET2 protein turnover. Direct regulator of TET2 stability. | Leukemia | Naderi et al., Hum. Reprod. Update. 2025. | |
| DNMT1 | Preserves methylation patterns after replication. Maintenance DNA methyltransferase that counterbalances TET activity. | AML, colorectal cancer, breast cancer | Hor et al., J. Endocrinol. 2024 | |
| DNMT3A | Establishes new methylation marks. De novo DNA methyltransferase antagonized by TET proteins. | AML, MDS, clonal hematopoiesis | Chatterjee et al., Cell. Mol. Biol. Lett. 2025. | |
| GADD45A | Promotes TET-mediated DNA demethylation and chromatin remodeling | Breast cancer, leukemia | Fengyuan et al., Chin. Med. J. 2026 | |
| HIF1A | Modulates DNA hydroxymethylation under low oxygen conditions. Links hypoxia signaling to TET activity. | Solid tumors, leukemia | Zhao et al., Neuroscience. 2025. | |
| IDH1 | Supports TET catalytic activity indirectly. DNA demethylation through metabolite production. Produces α-ketoglutarate (α-KG), an essential TET cofactor. | Supports TET catalytic activity indirectly. DNA demethylation through metabolite production. Produces α-ketoglutarate (α-KG), an essential TET cofactor. | Hoogstrate., Cell Rep. Med. 2026 | |
| NANOG | Maintains stem-cell-specific epigenetic states. Recruits TET proteins to pluripotency genes. | Germ cell tumors, stem cell dysregulation disorders | Lazaro-Carot et al., iScience. 2025. | |
| OCT4 (POU5F1) | Regulates DNA demethylation at developmental loci. Cooperates with TET1/TET2 in pluripotent stem cells | Germ cell tumors | Pantier et al., EMBO J. 2025 | |
| OGT (O-GlcNAc Transferase) | Coordinates DNA demethylation with histone modification. Forms a stable complex with TET proteins. | Cancer, diabetes, neurodegenerative disorders | Maejima et al., Aging Cell. 2025 | |
| PARP1 | Facilitates access to methylated DNA and DNA repair by interactign with TET. | Breast cancer, ovarian cancer | Ho et al., Nature Communication. 2025 | |
| SIN3A | Coordinates chromatin remodeling and gene repression. Transcriptional co-regulator. | Breast cancer, AML | Liang et al., MedComm. 2025. | |
| SOX2 | Controls enhancer demethylation and activation. Partners with TET proteins at stem-cell enhancers. | Glioblastoma, developmental disorders | Ebert et al., SSCR. 2025. | |
| TDG (Thymine DNA Glycosylase) | Completes active DNA demethylation through base excision repair. Removes TET-generated 5fC and 5caC intermediates. | Colorectal cancer, developmental disorders | Kang et al., Biomol Ther (Seoul). 2025. | |
| TET1, TET2, TET3 | Active DNA demethylation, pluripotency and developmental gene expression. Epigenetic homeostasis in hematopoietic stem cells. Epigenetic reprogramming during development and differentiation. Core dioxygenase that oxidizes 5mC to 5hmC, 5fC, and 5caC. | Breast cancer, colon cancer, neurodevelopmental disorders, myelodysplastic syndrome (MDS), clonal hematopoiesis, lymphoma, developmental delay, and intellectual disability. | Wu et al., Front. Endocrinol., 2025 | |
| UHRF1 | Balances methylation inheritance and demethylation. DNA methylation maintenance factor that interfaces with TET machinery. | Hepatocellular carcinoma, leukemia | Harris et al., Sci. Adv. 2025 | |
| WT1 | Directs locus-specific DNA demethylation. Recruits TET2 to target genes. | Wilms tumor, AML | Tian et al., Science Bulletin 70. 2025 |
Additional Resources
