ArticleGenome biology2014
Global loss of DNA methylation uncovers intronic enhancers in genes showing expression changes.
Article in Genome biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers.
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Who cites it
107 citing papers in PubMed, 171 citations in OpenAlex.
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- Biological age construction for prediction of mortality in the Chinese population.GeroScience · 2025Article
- Reliable investigation of DNA methylation using Oxford nanopore technologies.Scientific reports · 2025Article
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- Molecular Regulation of Palatogenesis and Clefting: An Integrative Analysis of Genetic, Epigenetic Networks, and Environmental Interactions.International journal of molecular sciences · 2025Review
- Motif distribution and DNA methylation underlie distinct Cdx2 binding during development and homeostasis.Nature communications · 2025Article
- A dual role of Cohesin in DNA DSB repair.Nature communications · 2025Article
- Acute myeloid leukemia-derived extracellular vesicles induced DNA methylation changes responsible for inflammatory program in normal hematopoietic stem progenitor cells.Frontiers in immunology · 2025Article
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- DNA methylation-dependent and -independent binding of CDX2 directs activation of distinct developmental and homeostatic genes.bioRxiv : the preprint server for biology · 2024Article
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- Methylation-directed regulatory networks determine enhancing and silencing of mutation disease driver genes and explain inter-patient expression variation.Genome biology · 2023Article
- Exploring the Effects of Rearing Densities on Epigenetic Modifications in the Zebrafish Gonads.International journal of molecular sciences · 2023Article
- The landscape of cryptic antisense transcription in human cancers reveals an oncogenic noncoding RNA in lung cancer.Science advances · 2023Article
- Myo1e overexpression in lung adenocarcinoma is associated with increased risk of mortality.Scientific reports · 2023Article
- Transcriptional reprogramming of skeletal muscle stem cells by the niche environment.Nature communications · 2023Article
- Diverse silent chromatin states modulate genome compartmentalization and loop extrusion barriers.Nature structural & molecular biology · 2023Article
- Active DNA demethylation of developmentalScience advances · 2022Article
47 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
7 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundGene expression is epigenetically regulated by a combination of histone modifications and methylation of CpG dinucleotides in promoters. In normal cells, CpG-rich promoters are typically unmethylated, marked with histone modifications such as H3K4me3, and are highly active. During neoplastic transformation, CpG dinucleotides of CG-rich promoters become aberrantly methylated, corresponding with the removal of active histone modifications and transcriptional silencing. Outside of promoter regions, distal enhancers play a major role in the cell type-specific regulation of gene expression. Enhancers, which function by bringing activating complexes to promoters through chromosomal looping, are also modulated by a combination of DNA methylation and histone modifications.
resultsHere we use HCT116 colorectal cancer cells with and without mutations in DNA methyltransferases, the latter of which results in a 95% reduction in global DNA methylation levels. These cells are used to study the relationship between DNA methylation, histone modifications, and gene expression. We find that the loss of DNA methylation is not sufficient to reactivate most of the silenced promoters. In contrast, the removal of DNA methylation results in the activation of a large number of enhancer regions as determined by the acquisition of active histone marks.
conclusionsAlthough the transcriptome is largely unaffected by the loss of DNA methylation, we identify two distinct mechanisms resulting in the upregulation of distinct sets of genes. One is a direct result of DNA methylation loss at a set of promoter regions and the other is due to the presence of new intragenic enhancers.
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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.