ArticleGenome research2019
New guidelines for DNA methylome studies regarding 5-hydroxymethylcytosine for understanding transcriptional regulation.
Article in Genome research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed.
- Postnatal conversion of methylcytosine to hydroxymethylcytosine reconfigures the human neuronal epigenome.bioRxiv : the preprint server for biology · 2026Article
- DMN-seq enriches DNA hypomethylated regions for biomarker discovery using 5-methylcytosine glycosylase.Genome biology · 2026Article
- Integrative dual ctDNA 5mC/5hmC methylomics and clonal reconstruction infer tumor transcription and resistance phenotypes in metastatic prostate cancer.Research square · 2026Article
- 5mC and 5hmC methylation sequencing: the power of 6-base sequencing in a multiomic era.Epigenomics · 2026Review
- Environmental Toxicants in the Hispanic Community Epigenetically Contributing to Preeclampsia.Cardiovascular toxicology · 2025Review
- METTL3-mediated mMolecular biology reports · 2025Review
- Towards universal modeling of transcript isoform expression levels.bioRxiv : the preprint server for biology · 2025Article
- From Lineage to Longevity: A Field Guide to the Key Players in Epigenetic Contribution to Offspring Health.Current issues in molecular biology · 2025Review
- DNA methylation confers a cerebellum-specific identity in non-human primates.Zoological research · 2025Article
- DNA methylation profiling identifies TBKBP1 as potent amplifier of cytotoxic activity in CMV-specific human CD8+ T cells.PLoS pathogens · 2024Article
- Epigenetic and Genetic Differentiation Between Coregonus Species Pairs.Genome biology and evolution · 2024Article
- Article
- New genetic and epigenetic insights into the chemokine system: the latest discoveries aiding progression toward precision medicine.Cellular & molecular immunology · 2023Review
- DNA methylation markers for kidney function and progression of diabetic kidney disease.Nature communications · 2023Article
- A pilot investigation of differential hydroxymethylation levels in patient-derived neural stem cells implicates altered cortical development in bipolar disorder.Frontiers in psychiatry · 2023Article
- Recent advances in understanding DNA methylation of prostate cancer.Frontiers in oncology · 2023Review
- Epigenetic and transcriptomic reprogramming in monocytes of severe COVID-19 patients reflects alterations in myeloid differentiation and the influence of inflammatory cytokines.Genome medicine · 2022Article
- The 5-Hydroxymethylcytosine Landscape of Prostate Cancer.Cancer research · 2022Article
- Article
- The Epigenetics of Psychosis: A Structured Review with Representative Loci.Biomedicines · 2022Review
Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Many DNA methylome profiling methods cannot distinguish between 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC). Because 5mC typically acts as a repressive mark whereas 5hmC is an intermediate form during active demethylation, the inability to separate their signals could lead to incorrect interpretation of the data. Is the extra information contained in 5hmC signals worth the additional experimental and computational costs? Here we combine whole-genome bisulfite sequencing (WGBS) and oxidative WGBS (oxWGBS) data in various human tissues to investigate the quantitative relationships between gene expression and the two forms of DNA methylation at promoters, transcript bodies, and immediate downstream regions. We find that 5mC and 5hmC signals correlate with gene expression in the same direction in most samples. Considering both types of signals increases the accuracy of expression levels inferred from methylation data by a median of 18.2% as compared to having only WGBS data, showing that the two forms of methylation provide complementary information about gene expression. Differential analysis between matched tumor and normal pairs is particularly affected by the superposition of 5mC and 5hmC signals in WGBS data, with at least 25%-40% of the differentially methylated regions (DMRs) identified from 5mC signals not detected from WGBS data. Our results also confirm a previous finding that methylation signals at transcript bodies are more indicative of gene expression levels than promoter methylation signals. Overall, our study provides data for evaluating the cost-effectiveness of some experimental and analysis options in the study of DNA methylation in normal and cancer samples.
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