ArticleProceedings of the National Academy of Sciences of the United States of America2011
Reprogramming of the paternal genome upon fertilization involves genome-wide oxidation of 5-methylcytosine.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 321 papers.
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Who cites it
321 citing papers in PubMed, 677 citations in OpenAlex.
- Article
- DNA Methylation Dynamics in Development and Disease: Insights from Zebrafish Models.Biomedicines · 2026Review
- Maternal O-GlcNAc Transferase Is Required for the Asymmetry of Epigenetic Modifications in Mouse Zygotes.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- 5-Hydroxymethylcytosine Dynamics Reveals Coordinated Reprogramming of Parental Genomes and X Chromosome Dosage Balance in Mouse SCNT Embryos.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Loss of TET2 activity limits the ability of vitamin C to activate DNA demethylation in human HAP1 cells.Epigenetics & chromatin · 2025Article
- 5-hydroxymethylcytosine analysis reveals stable epigenomic changes in tumor tissue that enable cancer detection in cell-free DNA.Communications biology · 2025Article
- Mutational disruption of transcription factors binding and regulatory networks in a case of unexplained total fertilization failure.Journal of translational medicine · 2025Article
- Ten-Eleven Translocation Family Proteins: Structure, Biological Functions, Diseases, and Targeted Therapy.MedComm · 2025Review
- DNA methylation mechanisms in the maturing and ageing oocyte.Epigenetics & chromatin · 2025Review
- Article
- Male gamete copies to characterize genome inheritance and generate progenies.Scientific reports · 2025Article
- TET3 regulates hematopoietic stem cell homeostasis during embryonic and adult hematopoiesis.HemaSphere · 2025Article
- Molecular genetic testing and cohort analysis of 32 twin pairs with neurodevelopmental disorders-Reporting a novel de novo variant of TET3.Human genomics · 2025Article
- Telomere length in offspring is determined by mitochondrial-nuclear communication at fertilization.Nature communications · 2025Article
- Predicting differentially methylated cytosines in TET and DNMT3 knockout mutants via a large language model.Briefings in bioinformatics · 2025Article
- Exploring the Epigenetic Landscape of Spermatozoa: Impact of Oxidative Stress and Antioxidant Supplementation on DNA Methylation and Hydroxymethylation.Antioxidants (Basel, Switzerland) · 2024Article
- 5-Formylcytosine: a new epigenetic player.Signal transduction and targeted therapy · 2024Article
- Epigenetic modifications in hematopoietic ecosystem: a key tuner from homeostasis to acute myeloid leukemia.Blood science (Baltimore, Md.) · 2024Review
- Predicting Differentially Methylated Cytosines in TET and DNMT3 Knockout Mutants via a Large Language Model.bioRxiv : the preprint server for biology · 2024Article
- The Role of DNMT Methyltransferases and TET Dioxygenases in the Maintenance of the DNA Methylation Level.Biomolecules · 2024Review
261 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Genome-wide erasure of DNA cytosine-5 methylation has been reported to occur along the paternal pronucleus in fertilized oocytes in an apparently replication-independent manner, but the mechanism of this reprogramming process has remained enigmatic. Recently, considerable amounts of 5-hydroxymethylcytosine (5hmC), most likely derived from enzymatic oxidation of 5-methylcytosine (5mC) by TET proteins, have been detected in certain mammalian tissues. 5hmC has been proposed as a potential intermediate in active DNA demethylation. Here, we show that in advanced pronuclear-stage zygotes the paternal pronucleus contains substantial amounts of 5hmC but lacks 5mC. The converse is true for the maternal pronucleus, which retains 5mC but shows little or no 5hmC signal. Importantly, 5hmC persists into mitotic one-cell, two-cell, and later cleavage-stage embryos, suggesting that 5mC oxidation is not followed immediately by genome-wide removal of 5hmC through excision repair pathways or other mechanisms. This conclusion is supported by bisulfite sequencing data, which shows only limited conversion of modified cytosines to cytosines at several gene loci. It is likely that 5mC oxidation is carried out by the Tet3 oxidase. Tet3, but not Tet1 or Tet2, was expressed at high levels in oocytes and zygotes, with rapidly declining levels at the two-cell stage. Our results show that 5mC oxidation is part of the early life cycle of mammals.
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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.