ArticlePLoS genetics2014
Hydroxymethylated cytosines are associated with elevated C to G transversion rates.
Article in PLoS genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed, 37 citations in OpenAlex.
- A complex mutational signature generated by cytarabine resistance.NAR cancer · 2026Article
- Genotype-dependent DNA methylation patterns are negatively associated with allelic variation rather than heat-induced gene expression in two contrasting potato genotypes.The Plant journal : for cell and molecular biology · 2026Article
- Epigenetic mechanisms of rapid-acting antidepressants.Translational psychiatry · 2024Review
- Mutation rate heterogeneity at the sub-gene scale due to local DNA hypomethylation.Nucleic acids research · 2024Article
- DNA hydroxymethylation differences underlie phenotypic divergence of somatic growth in Nile tilapia reared in common garden.Epigenetics · 2023Article
- Developmental exposures to common environmental contaminants, DEHP and lead, alter adult brain and blood hydroxymethylation in mice.Frontiers in cell and developmental biology · 2023Article
- Mutational Signatures of Replication Timing and Epigenetic Modification Persist through the Global Divergence of Mutation Spectra across the Great Ape Phylogeny.Genome biology and evolution · 2022Article
- The origin of human mutation in light of genomic data.Nature reviews. Genetics · 2021Review
- Genome-Wide Analysis of Cadmium-Induced, Germline Mutations in a Long-TermEnvironmental health perspectives · 2021Article
- Population sequencing data reveal a compendium of mutational processes in the human germ line.Science (New York, N.Y.) · 2021Article
- An epigenomic landscape of cervical intraepithelial neoplasia and cervical cancer using single-base resolution methylome and hydroxymethylome.Clinical and translational medicine · 2021Article
- Ten-eleven translocation protein 1 modulates medulloblastoma progression.Genome biology · 2021Article
- Active DNA demethylation-The epigenetic gatekeeper of development, immunity, and cancer.Advanced genetics (Hoboken, N.J.) · 2021Review
- Epigenetic Regulation of Genomic Stability by Vitamin C.Frontiers in genetics · 2021Review
- Cytosine Methylation Affects the Mutability of Neighboring Nucleotides in Germline and Soma.Genetics · 2020Article
- TET enzymes control antibody production and shape the mutational landscape in germinal centre B cells.The FEBS journal · 2019Article
- Gene promoter and exon DNA methylation changes in colon cancer development - mRNA expression and tumor mutation alterations.BMC cancer · 2018Article
- DIRECTION: a machine learning framework for predicting and characterizing DNA methylation and hydroxymethylation in mammalian genomes.Bioinformatics (Oxford, England) · 2017Article
- Review
- Alternative roles for oxidized mCs and TETs.Current opinion in genetics & development · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 3 countries.
Funding
Abstract
It has long been known that methylated cytosines deaminate at higher rates than unmodified cytosines and constitute mutational hotspots in mammalian genomes. The repertoire of naturally occurring cytosine modifications, however, extends beyond 5-methylcytosine to include its oxidation derivatives, notably 5-hydroxymethylcytosine. The effects of these modifications on sequence evolution are unknown. Here, we combine base-resolution maps of methyl- and hydroxymethylcytosine in human and mouse with population genomic, divergence and somatic mutation data to show that hydroxymethylated and methylated cytosines show distinct patterns of variation and evolution. Surprisingly, hydroxymethylated sites are consistently associated with elevated C to G transversion rates at the level of segregating polymorphisms, fixed substitutions, and somatic mutations in tumors. Controlling for multiple potential confounders, we find derived C to G SNPs to be 1.43-fold (1.22-fold) more common at hydroxymethylated sites compared to methylated sites in human (mouse). Increased C to G rates are evident across diverse functional and sequence contexts and, in cancer genomes, correlate with the expression of Tet enzymes and specific components of the mismatch repair pathway (MSH2, MSH6, and MBD4). Based on these and other observations we suggest that hydroxymethylation is associated with a distinct mutational burden and that the mismatch repair pathway is implicated in causing elevated transversion rates at hydroxymethylated cytosines.
Indexed as
Identifiers
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.