ArticleProceedings of the National Academy of Sciences of the United States of America2017
5-hydroxymethylcytosine accumulation in postmitotic neurons results in functional demethylation of expressed genes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers, 1 of them a synthesis that pooled it.
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
88 citing papers in PubMed, 1 synthesis or guideline pooled it, 155 citations in OpenAlex.
- Active Demethylation of Non-CpG Moieties in Animals: A Neglected Research Area.International journal of molecular sciences · 2019Pooled it
- Whole-genome 5-hydroxymethylation profiling of human neurons for regulatory and biological insight.Epigenetics & chromatin · 2026Article
- Neural stem cell epigenomes and fate bias are temporally coordinated during mouse cortical development.Genes & development · 2026Article
- Postnatal conversion of methylcytosine to hydroxymethylcytosine reconfigures the human neuronal epigenome.bioRxiv : the preprint server for biology · 2026Article
- Review
- Active DNA demethylation upstream of rod-photoreceptor fate determination is required for retinal development.PLoS biology · 2025Article
- Exploring the complexity of MECP2 function in Rett syndrome.Nature reviews. Neuroscience · 2025Review
- DNA Methylation in Long-Term Memory.Physiology (Bethesda, Md.) · 2025Review
- Coordinated neuron-specific splicing events restrict nucleosome engagement of the LSD1 histone demethylase complex.Cell reports · 2025Article
- Review
- Article
- 3,N4-Etheno-5-methylcytosine blocks TET1-3 oxidation but is repaired by ALKBH2, 3 and FTO.Nucleic acids research · 2024Article
- TET3-overexpressing macrophages promote endometriosis.The Journal of clinical investigation · 2024Article
- Loss of TET Activity in the Postnatal Mouse Brain Perturbs Synaptic Gene Expression and Impairs Cognitive Function.Neuroscience bulletin · 2024Article
- Injured inflammatory environment overrides the TET2 shaped epigenetic landscape of pluripotent stem cell derived human neural stem cells.Scientific reports · 2024Article
- Parkinson's disease-associated shifts between DNA methylation and DNA hydroxymethylation in human brain in PD-related genes, including PARK19 (DNAJC6) and PTPRN2 (IA-2β).Research square · 2024Article
- Region-specific DNA hydroxymethylation along the malignant progression of IDH-mutant gliomas.Cancer science · 2024Article
- Overcoming genetic and cellular complexity to study the pathophysiology of X-linked intellectual disabilities.Journal of neurodevelopmental disorders · 2024Review
- TDP-43 chronic deficiency leads to dysregulation of transposable elements and gene expression by affecting R-loop and 5hmC crosstalk.Cell reports · 2024Article
- Differential usage of DNA modifications in neurons, astrocytes, and microglia.Epigenetics & chromatin · 2023Article
28 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
5-hydroxymethylcytosine (5hmC) occurs at maximal levels in postmitotic neurons, where its accumulation is cell-specific and correlated with gene expression. Here we demonstrate that the distribution of 5hmC in CG and non-CG dinucleotides is distinct and that it reflects the binding specificity and genome occupancy of methylcytosine binding protein 2 (MeCP2). In expressed gene bodies, accumulation of 5hmCG acts in opposition to 5mCG, resulting in "functional" demethylation and diminished MeCP2 binding, thus facilitating transcription. Non-CG hydroxymethylation occurs predominantly in CA dinucleotides (5hmCA) and it accumulates in regions flanking active enhancers. In these domains, oxidation of 5mCA to 5hmCA does not alter MeCP2 binding or expression of adjacent genes. We conclude that the role of 5-hydroxymethylcytosine in postmitotic neurons is to functionally demethylate expressed gene bodies while retaining the role of MeCP2 in chromatin organization.
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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.