ArticleGenome biology2013
DNA methylation of distal regulatory sites characterizes dysregulation of cancer genes.
Article in Genome biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 215 papers, 2 of them syntheses that pooled it.
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215 citing papers in PubMed, 2 syntheses or guidelines pooled it, 364 citations in OpenAlex.
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- The polymorphism of rs266729 in adiponectin gene and type 2 diabetes mellitus: A Meta-Analysis.Medicine · 2017Pooled it
- Specific molecular signatures predict decitabine response in chronic myelomonocytic leukemia.The Journal of clinical investigation · 2015Trial
- Whole-genome DNA methylation analysis reveals distinct subtype characteristics in epithelial ovarian cancer.Cancer gene therapy · 2026Article
- Recurrent mechanisms of biallelic epigenetic inactivation reveal new putative tumour suppressor genes in prostate cancer.Nature communications · 2026Article
- Blood-Based DNA Methylation Models Improve Short-term Cardiovascular Risk Stratification in Individuals With Type 2 Diabetes.Diabetes care · 2026Article
- Genome-wide DNA methylation profiling of triple-negative breast cancer uncovers epigenetic biomarkers of tumor identity and the immune microenvironment.NPJ breast cancer · 2026Article
- Epigenome-wide DNA methylation patterns associated with disease activity in systemic lupus erythematosus.Scientific reports · 2026Article
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- DNA Methylation in Blood Samples from Malignant Mammary Tumors of Companion Dogs: A Pilot Study.Computational and structural biotechnology journal · 2026Article
- Methylation reprogramming associated with aggressive prostate cancer and ancestral disparities.Molecular systems biology · 2025Article
- Brain DNA Methylation Atlas of AppAging cell · 2025Article
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- Tracing regulatory element networks using epigenetic traits to identify key transcription factors: TENET R/Bioconductor package.Bioinformatics (Oxford, England) · 2025Article
- Prediction of target genes and functional types of cis-regulatory modules in the human genome reveals their distinct properties.BMC biology · 2025Article
- Epigenetics: A link between toxicants and diseases.iScience · 2025Review
- Association of Intergenic and IntragenicInternational journal of molecular sciences · 2025Article
- Cell-type-specific subtyping of epigenomes improves prognostic stratification of cancer.Genome medicine · 2025Article
- The DNA methylation landscape of primary triple-negative breast cancer.Nature communications · 2025Article
155 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAbnormal epigenetic marking is well documented in gene promoters of cancer cells, but the study of distal regulatory siteshas lagged behind.We performed a systematic analysis of DNA methylation sites connected with gene expression profilesacross normal and cancerous human genomes.
resultsUtilizing methylation and expression data in 58 cell types, we developed a model for methylation-expression relationships in gene promoters and extrapolated it to the genome. We mapped numerous sites at which DNA methylation was associated with expression of distal genes. These sites bind transcription factors in a methylation-dependent manner, and carry the chromatin marks of a particular class of transcriptional enhancers. In contrast to the traditional model of one enhancer site per cell type, we found that single enhancer sites may define gradients of expression levels across many different cell types. Strikingly, the identified sites were drastically altered in cancers: hypomethylated enhancer sites associated with upregulation of cancer-related genes and hypermethylated sites with downregulation. Moreover, the association between enhancer methylation and gene deregulation in cancerwas significantly stronger than the association of promoter methylationwith gene deregulation.
conclusionsMethylation of distal regulatory sites is closely related to gene expression levels across the genome. Single enhancers may modulate ranges of cell-specific transcription levels, from constantlyopen promoters. In contrast to the remote relationships between promoter methylation and gene dysregulation in cancer, altered methylation of enhancer sites is closely related to gene expression profiles of transformed cells.
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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.