ArticleNature2011
Dynamic regulation of 5-hydroxymethylcytosine in mouse ES cells and during differentiation.
Article in Nature, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 609 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.
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Who cites it
609 citing papers in PubMed, 1,140 citations in OpenAlex.
- DNA methylation-mediated suppression of endocytosis confers resistance to duck hepatitis A virus type 3.Microbiology spectrum · 2026Article
- Chromatin binding and N-terminal domains of DNMT3B1 confer specificity for developmentally regulated CpG island methylation.Genes & development · 2026Article
- HM-DyadCap - capture and mapping of 5-hydroxymethylcytosine/5-methylcytosine CpG dyads in mammalian DNA.Nucleic acids research · 2026Article
- Sequencing DNA methylation and hydroxymethylation at co-occurring chromatin features.Nature communications · 2026Article
- Chromatin Remodeling in VSMC Phenotype Switching During Vascular Remodeling: From Mechanism to Therapeutic Potential.Biomolecules · 2026Review
- The role of cytosine modification symmetry in mammalian epigenome regulation.Chemical science · 2026Review
- 5-methylcytosine and 5-hydroxymethylcytosine are synergistic biomarkers for early detection of colorectal cancer.Communications medicine · 2026Article
- Multidimensional regulatory mechanisms and translational potential of epigenetic networks in the rheumatoid arthritis disease course.Frontiers in immunology · 2026Review
- The rs713586 risk variant dysregulates ADCY3 rather than DNAJC27, leading to obesity through ZFP42-TET1-mediated DNA methylation.EBioMedicine · 2026Article
- The nuclear and mitochondrial genomes need to tango. How is their dance synchronized during development?NAR molecular medicine · 2026Article
- TRIM37-PARP1-TET1 axis maintains stemness and prevents osteoporosis by inhibiting DNMT1 alternative splicing via 5hmC regulation.Nature communications · 2025Article
- 5-hydroxymethylcytosine analysis reveals stable epigenomic changes in tumor tissue that enable cancer detection in cell-free DNA.Communications biology · 2025Article
- 5-Hydroxymethylcytosine: a key epigenetic mark in cancer and chemotherapy response.Epigenetics & chromatin · 2025Review
- Distinct roles of TET-mediated cytosine oxidation in neural stem cell fate decisions.Stem cell reports · 2025Article
- SCoTCH-seq reveals that 5-hydroxymethylcytosine encodes regulatory information across DNA strands.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Fundamentals of DNA methylation in development.Pediatric research · 2025Review
- Article
- Screening of pivotal oncogenes modulated by DNA methylation in hepatocellular carcinoma and identification of atractylenolide I as an anti-cancer drug.Human cell · 2025Article
- Pioneering contribution of Professor Bruce Ames to early development in biochemical aspects of oxidatively generated damage to DNA.Frontiers in molecular biosciences · 2025Review
- Coupling of stemness maintenance with cell cycle control in stem cells.Frontiers in cell and developmental biology · 2025Review
549 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Methylation at the 5' position of cytosine in DNA has important roles in genome function and is dynamically reprogrammed during early embryonic and germ cell development. The mammalian genome also contains 5-hydroxymethylcytosine (5hmC), which seems to be generated by oxidation of 5-methylcytosine (5mC) by the TET family of enzymes that are highly expressed in embryonic stem (ES) cells. Here we use antibodies against 5hmC and 5mC together with high throughput sequencing to determine genome-wide patterns of methylation and hydroxymethylation in mouse wild-type and mutant ES cells and differentiating embryoid bodies. We find that 5hmC is mostly associated with euchromatin and that whereas 5mC is under-represented at gene promoters and CpG islands, 5hmC is enriched and is associated with increased transcriptional levels. Most, if not all, 5hmC in the genome depends on pre-existing 5mC and the balance between these two modifications is different between genomic regions. Knockdown of Tet1 and Tet2 causes downregulation of a group of genes that includes pluripotency-related genes (including Esrrb, Prdm14, Dppa3, Klf2, Tcl1 and Zfp42) and a concomitant increase in methylation of their promoters, together with an increased propensity of ES cells for extraembryonic lineage differentiation. Declining levels of TETs during differentiation are associated with decreased hydroxymethylation levels at the promoters of ES cell-specific genes together with increased methylation and gene silencing. We propose that the balance between hydroxymethylation and methylation in the genome is inextricably linked with the balance between pluripotency and lineage commitment.
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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.