ArticleGenome biology2022
Large-scale manipulation of promoter DNA methylation reveals context-specific transcriptional responses and stability.
Article in Genome biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 1 of them a synthesis that pooled it.
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Who cites it
73 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Evidence on the link between hypothyroidism and non-alcoholic fatty liver disease: an updated systematic review.BMC endocrine disorders · 2025Pooled it
- Elevated DNA 5-hydroxymethylation promotes chondrocyte differentiation via TET-mediated epigenetic downregulation of hTERT in human mesenchymal stem cells.Histochemistry and cell biology · 2026Article
- A Comparative Analysis of the Methylation Status of Non-Coding RNA Promoters in Fibroid and Matched Myometrium.International journal of molecular sciences · 2026Article
- Influence of Genetic and Epigenetic Factors on Periodontitis Susceptibility and Treatment Outcomes.Biochemical genetics · 2026Review
- Neural stem cells as potential mediators of prenatal dietary stress through epigenetic mechanisms.Stem cell reports · 2026Article
- Two Decades of DNA Methylation Shifts Reveal Epigenomic Responses to Environmental Change in Wild Salmo salar From Its Southernmost Populations.Molecular ecology · 2026Article
- High-Glucose-Induced Metabolic and Epithelial Stress in Grass Carp Intestinal Epithelial Cells Associated with Methylation-Related Transcriptional Responses.International journal of molecular sciences · 2026Article
- Transcriptomic regulation of pancreatic acinar cell homeostasis and plasticity.Biochemical Society transactions · 2026Review
- Transcriptional Bursting in Pluripotent Stem Cells.Biology · 2026Review
- Glatiramer Acetate Therapy Induces DNA Methylation Changes in Immune Cells of Multiple Sclerosis Patients: A Pilot Study.International journal of molecular sciences · 2026Article
- Epigenetic Modulation of the ACE System Underlies the Slow Aerobic Muscle Phenotype and Metabolic Exercise Response.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Identification of cis-regulatory elements provides insights into tissue-specific gene regulation in the sheep genome.Nature communications · 2026Article
- Systematic investigation of interindividual variation of DNA methylation in human whole blood.Genome biology · 2026Article
- Methylome and Transcriptome Analysis Reveals Differences in Callus Development and Plantlet Regeneration Capacity Between TwoPlants (Basel, Switzerland) · 2026Article
- BayesPI-FLY: a Bayesian neural network approach for inferring feature weighted TF-DNA interaction.Briefings in bioinformatics · 2026Article
- Epigenetic editing: from concept to clinic.Nature reviews. Drug discovery · 2026Review
- Isoform-specific single-cell perturb-seq reveals distinct functions of alternative promoters in drug response.Nucleic acids research · 2026Article
- Article
- Promoter Methylation-Expression Coupling of Gliogenesis Genes inInternational journal of molecular sciences · 2026Article
- Epigenetic editing of marine medaka (Zoological research · 2026Article
13 more citing papers are in PubMed but not listed here.
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13 authors.
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Abstract
backgroundCytosine DNA methylation is widely described as a transcriptional repressive mark with the capacity to silence promoters. Epigenome engineering techniques enable direct testing of the effect of induced DNA methylation on endogenous promoters; however, the downstream effects have not yet been comprehensively assessed.
resultsHere, we simultaneously induce methylation at thousands of promoters in human cells using an engineered zinc finger-DNMT3A fusion protein, enabling us to test the effect of forced DNA methylation upon transcription, chromatin accessibility, histone modifications, and DNA methylation persistence after the removal of the fusion protein. We find that transcriptional responses to DNA methylation are highly context-specific, including lack of repression, as well as cases of increased gene expression, which appears to be driven by the eviction of methyl-sensitive transcriptional repressors. Furthermore, we find that some regulatory networks can override DNA methylation and that promoter methylation can cause alternative promoter usage. DNA methylation deposited at promoter and distal regulatory regions is rapidly erased after removal of the zinc finger-DNMT3A fusion protein, in a process combining passive and TET-mediated demethylation. Finally, we demonstrate that induced DNA methylation can exist simultaneously on promoter nucleosomes that possess the active histone modification H3K4me3, or DNA bound by the initiated form of RNA polymerase II.
conclusionsThese findings have important implications for epigenome engineering and demonstrate that the response of promoters to DNA methylation is more complex than previously appreciated.
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