ArticleEpigenetics & chromatin2014
Meta-analysis of human methylomes reveals stably methylated sequences surrounding CpG islands associated with high gene expression.
Article in Epigenetics & chromatin, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 2 of them syntheses that pooled it.
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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
56 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Epigenetic mechanisms in Tendon Ageing.British medical bulletin · 2020Pooled it
- An empirically driven data reduction method on the human 450K methylation array to remove tissue specific non-variable CpGs.Clinical epigenetics · 2017Pooled it
- Cell-free DNA methylome and fragmentome analysis for relapse monitoring of Ewing sarcoma.EMBO molecular medicine · 2026Article
- Epigenetic Potential and Dispersal Propensity in a Free-Living Songbird: A Spatial and Temporal Approach.Molecular ecology · 2025Article
- Fundamentals of DNA methylation in development.Pediatric research · 2025Review
- Complete reference genome and pangenome improve genome-wide detection and interpretation of DNA methylation using sequencing and array data.Cell reports · 2025Article
- Assessing DNA methylation detection for primary human tissue using Nanopore sequencing.Genome research · 2025Article
- Genome-wide methylome-based molecular pathologies associated with depression and suicide.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- DNA methylation profiles of cancer-related fatigue associated with markers of inflammation and immunometabolism.Molecular psychiatry · 2025Article
- Glioma immune microenvironment composition calculator (GIMiCC): a method of estimating the proportions of eighteen cell types from DNA methylation microarray data.Acta neuropathologica communications · 2024Article
- Review
- Simultaneous assessment of human genome and methylome data in a single experiment using limited deamination of methylated cytosine.Genome research · 2024Article
- Decoding the Epigenetic Landscape: Insights into 5mC and 5hmC Patterns in Mouse Cortical Cell Types.bioRxiv : the preprint server for biology · 2024Article
- A cfDNA methylation-based tissue-of-origin classifier for cancers of unknown primary.Nature communications · 2024Article
- Assessing methylation detection for primary human tissue using Nanopore sequencing.bioRxiv : the preprint server for biology · 2024Article
- Article
- DNA methylome profiling in occupational radon exposure miners using an Illumina Infinium Methylation EPIC BeadChip.Toxicology research · 2023Article
- Nrf2Frontiers in genetics · 2023Article
- Context-dependent CpG methylation directs cell-specific binding of transcription factor ZBTB38.Epigenetics · 2022Article
- MC profiling: a novel approach to analyze DNA methylation heterogeneity in genome-wide bisulfite sequencing data.NAR genomics and bioinformatics · 2022Article
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
backgroundDNA methylation is thought to play an important role in the regulation of mammalian gene expression, partly based on the observation that a lack of CpG island methylation in gene promoters is associated with high transcriptional activity. However, the CpG island methylation level only accounts for a fraction of the variance in gene expression, and methylation in other domains is hypothesized to play a role. We hypothesized that regions of very high stability in methylation would exist and provide biological insight into the role of methylation both within and outside CpG islands.
resultsWe set out to identify highly stable regions in the human methylome, based on the subset of CpGs assayed with an Illumina Infinium 450 K array. Using 1,737 samples from 30 publically available studies, we identified 15,224 CpGs that are 'ultrastable' in their state across tissues and developmental stages (974 always methylated; 14,250 always unmethylated). Further analysis of ultrastable CpGs led us to identify a novel subset of CpG islands, 'ravines', which exhibit a markedly consistent pattern of low methylation with highly methylated flanking shores and shelves. We distinguish ravines from other CpG islands characterized by a broader flanking region of low methylation. Interestingly, ravines are associated with higher gene expression compared to typical unmethylated CpG islands, and are more often found near housekeeping genes.
conclusionsThe identification of ultrastable sites in the human methylome led us to identify a subclass of CpG islands characterized by a very stable pattern of methylation encompassing the island and flanking regions, established early in development and maintained through differentiation. This pattern is associated with particularly high levels of gene expression, providing new evidence that methylation beyond the CpG island could play a role in gene expression.
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Registered trials
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