ArticleNature genetics2018
TET proteins safeguard bivalent promoters from de novo methylation in human embryonic stem cells.
Article in Nature genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 132 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
132 citing papers in PubMed, 207 citations in OpenAlex.
- Live-cell DNMT3A "catalysome" mapping using engineered methyl-transfer pathways.Nucleic acids research · 2026Article
- DNA methylation either antagonizes or promotes Polycomb recruitment at transposable elements in Arabidopsis.Nature communications · 2026Article
- Article
- Sodium Butyrate-Assisted Induction of Posterior Pre-Neural Progenitors from Pluripotent Stem Cells.International journal of molecular sciences · 2026Article
- Mechanisms coordinating exit from the stem cell state in mammals.Genes & development · 2026Review
- Epigenetic activation of EBV BGLF4 determines antiviral-based regimen response in EBV+CNS lymphoproliferative disease.Blood neoplasia · 2026Article
- A tunable, ultrasensitive threshold in enzymatic activity governs the DNA methylation landscape.Biophysical journal · 2026Article
- DNA Methylation and Fetal Programming of Cardiovascular Disease: From Congenital Heart Diseases to Adult Cardiovascular Dysfunction.Reviews in cardiovascular medicine · 2026Review
- Why Does DNA Methylation Accumulate at CpG Loci?: Sequential Analysis ofActa histochemica et cytochemica · 2026Article
- Mechanisms of human germ cell development.Nature reviews. Molecular cell biology · 2026Review
- TET knockout cells transit between pluripotent states and exhibit precocious germline entry.The EMBO journal · 2025Article
- TET1 modulates trophoblast function by regulation of ODC1 in preeclampsia.Scientific reports · 2025Article
- Remodelling bivalent chromatin is essential for mouse peri-implantation embryogenesis.Nature cell biology · 2025Article
- Exploring the Antioxidant Roles of Cysteine and Selenocysteine in Cellular Aging and Redox Regulation.Biomolecules · 2025Review
- Ten-Eleven Translocation Family Proteins: Structure, Biological Functions, Diseases, and Targeted Therapy.MedComm · 2025Review
- Temporally discordant chromatin accessibility and DNA demethylation define short- and long-term enhancer regulation during cell fate specification.Cell reports · 2025Article
- Stage-specific DNA methylation dynamics in mammalian heart development.Epigenomics · 2025Review
- Histone bivalency in CNS development.Genes & development · 2025Review
- tet2 and tet3 regulate cell fate specification and differentiation events during retinal development.Scientific reports · 2025Article
- Interplay between pioneer transcription factors and epigenetic modifiers in cell reprogramming.Regenerative therapy · 2025Review
72 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
- Erratum issued
Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
Abstract
TET enzymes oxidize 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), which can lead to DNA demethylation. However, direct connections between TET-mediated DNA demethylation and transcriptional output are difficult to establish owing to challenges in distinguishing global versus locus-specific effects. Here we show that TET1, TET2 and TET3 triple-knockout (TKO) human embryonic stem cells (hESCs) exhibit prominent bivalent promoter hypermethylation without an overall corresponding decrease in gene expression in the undifferentiated state. Focusing on the bivalent PAX6 locus, we find that increased DNMT3B binding is associated with promoter hypermethylation, which precipitates a neural differentiation defect and failure of PAX6 induction during differentiation. dCas9-mediated locus-specific demethylation and global inactivation of DNMT3B in TKO hESCs partially reverses the hypermethylation at the PAX6 promoter and improves differentiation to neuroectoderm. Taking these findings together with further genome-wide methylation and TET1 and DNMT3B ChIP-seq analyses, we conclude that TET proteins safeguard bivalent promoters from de novo methylation to ensure robust lineage-specific transcription upon differentiation.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.