ArticleThe Journal of biological chemistry2011
Eicosapentaenoic acid demethylates a single CpG that mediates expression of tumor suppressor CCAAT/enhancer-binding protein delta in U937 leukemia cells.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 79 citations in OpenAlex.
- Interaction of methylation-related genetic variants with circulating fatty acids on plasma lipids: a meta-analysis of 7 studies and methylation analysis of 3 studies in the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium.The American journal of clinical nutrition · 2016Pooled it
- Adjunction of a fish oil emulsion to cytarabine and daunorubicin induction chemotherapy in high-risk AML.Scientific reports · 2022Trial
- Adherence to Mediterranean diet is associated with methylation changes in inflammation-related genes in peripheral blood cells.Journal of physiology and biochemistry · 2016Trial
- Epigenome-wide analysis of neonatal CD4(+) T-cell DNA methylation sites potentially affected by maternal fish oil supplementation.Epigenetics · 2014Trial
- DNA methylation pattern in overweight women under an energy-restricted diet supplemented with fish oil.BioMed research international · 2014Trial
- Decitabine-mediated DNA methylation dynamics at pericentromeric satellite 2 repeats.BMC cancer · 2025Article
- Differential DNA methylation and gene expression in stem cell-derived cardiomyocytes from patients with and without a history of clozapine-induced myocarditis.Journal of psychiatry & neuroscience : JPN · 2025Article
- Basic biology and roles of CEBPD in cardiovascular disease.Cell death discovery · 2025Review
- Dietary polyunsaturated fatty acids affect PPARγ promoter methylation status and regulate the PPARγ/COX2 pathway in some colorectal cancer cell lines.Genes & nutrition · 2025Article
- The feasibility of targeting macrophage for disease treatment: roles of CEBPD.Frontiers in immunology · 2025Review
- Interconnected Codons: Unravelling the Epigenetic Significance of Flanking Sequences in CpG Dyads.Journal of molecular evolution · 2024Article
- Physiologic and epigenetic effects of nutrients on disease pathways.Nutrition research and practice · 2023Article
- The Polyunsaturated Fatty Acid EPA, but Not DHA, Enhances Neurotrophic Factor Expression through Epigenetic Mechanisms and Protects against Parkinsonian Neuronal Cell Death.International journal of molecular sciences · 2022Article
- Prognostic Value, Immune Signature, and Molecular Mechanisms of the PHLDA Family in Pancreatic Adenocarcinoma.International journal of molecular sciences · 2022Article
- Article
- Azacitidine Omega-3 Self-Assemblies: Synthesis, Characterization, and Potent Applications for Myelodysplastic Syndromes.Pharmaceuticals (Basel, Switzerland) · 2021Article
- FABP7 Regulates Acetyl-CoA Metabolism Through the Interaction with ACLY in the Nucleus of Astrocytes.Molecular neurobiology · 2020Article
- Methylation status of CpG sites in the NOTCH4 promoter region regulates NOTCH4 expression in patients with tetralogy of Fallot.Molecular medicine reports · 2020Article
- How Dietary Factors Affect DNA Methylation: Lesson from Epidemiological Studies.Medicina (Kaunas, Lithuania) · 2020Review
- Polyunsaturated fatty acids and DNA methylation in colorectal cancer.World journal of clinical cases · 2019Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Polyunsaturated fatty acids (PUFAs) inhibit proliferation and induce differentiation in leukemia cells. To investigate the molecular mechanisms whereby fatty acids affect these processes, U937 leukemia cells were conditioned with stearic, oleic, linolenic, α-linolenic, arachidonic, eicosapentaenoic, and docosahexaenoic acids. PUFAs affected proliferation; eicosapentaenoic acid (EPA) was the most potent on cell cycle progression. EPA enhanced the expression of the myeloid lineage-specific transcription factors CCAAT/enhancer-binding proteins (C/EBPβ and C/EBPδ), PU.1, and c-Jun, resulting in increased expression of the monocyte lineage-specific target gene, the macrophage colony-stimulating factor receptor. Indeed, it is known that PU.1 and C/EBPs interact with their consensus sequences on a small DNA fragment of macrophage colony-stimulating factor receptor promoter, which is a determinant for expression. We demonstrated that C/EBPβ and C/EBPδ bind the same response element as a heterodimer. We focused on the enhanced expression of C/EBPδ, which has been reported to be a tumor suppressor gene silenced by promoter hypermethylation in U937 cells. After U937 conditioning with EPA and bisulfite sequencing of the -370/-20 CpG island on the C/EBPδ promoter region, we found a site-specific CpG demethylation that was a determinant for the binding activity of Sp1, an essential factor for C/EBPδ gene basal expression. Our results provide evidence for a new role of PUFAs in the regulation of gene expression. Moreover, we demonstrated for the first time that re-expression of the tumor suppressor C/EBPδ is controlled by the methylation state of a site-specific CpG dinucleotide.
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Registered trials
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.