ArticleBMC genomics2006
Epigenetics of gene expression in human hepatoma cells: expression profiling the response to inhibition of DNA methylation and histone deacetylation.
Article in BMC genomics, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
66 citing papers in PubMed, 1 synthesis or guideline pooled it, 148 citations in OpenAlex.
- Loss of alanine-glyoxylate and serine-pyruvate aminotransferase expression accelerated the progression of hepatocellular carcinoma and predicted poor prognosis.Journal of translational medicine · 2019Pooled it
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- Effect of CYP3A4 Methylation on Tacrolimus Pharmacokinetics.Therapeutic drug monitoring · 2025Article
- Investigating the Cellular Responses to Combined Nisin and Urolithin B Treatment (7:3) in HKB-11 Lymphoma Cells.International journal of molecular sciences · 2025Article
- A Review on New Frontiers in Drug-Drug Interaction Predictions and Safety Evaluations with In Vitro Cellular Models.Pharmaceutics · 2025Review
- Methylation-Mediated Silencing of miR-124-3 Regulates LRRC1 Expression and Promotes Oral Cancer Progression.Cancers · 2025Article
- Steroids and One-Carbon Metabolism: Clinical Implications in Endocrine Disorders.Neuroendocrinology · 2025Review
- Improvement of Monacolin K and Pigment Production inJournal of fungi (Basel, Switzerland) · 2024Article
- A universal co-expression gene network and prognostic model for hepatic-biliary-pancreatic cancers identified by integrative analyses.FEBS open bio · 2022Article
- Regulation of arsenic methylation: identification of the transcriptional region of the human AS3MT gene.Cell biology and toxicology · 2022Article
- Epigenetics in drug disposition & drug therapy: symposium report of the 24Drug metabolism reviews · 2022Review
- GATA6 is predicted to regulate DNA methylation in an in vitro model of human hepatocyte differentiation.Communications biology · 2022Article
- DNA Methylation Regulates a Set of Long Non-Coding RNAs Compromising Hepatic Identity during Hepatocarcinogenesis.Cancers · 2022Article
- CCAAT/Enhancer-Binding Proteins in Fibrosis: Complex Roles Beyond Conventional Understanding.Research (Washington, D.C.) · 2022Review
- The Central Role of Cytochrome P450 in Xenobiotic Metabolism-A Brief Review on a Fascinating Enzyme Family.Journal of xenobiotics · 2021Review
- Molecular effects and retinopathy induced by hydroxychloroquine during SARS-CoV-2 therapy: Role of CYP450 isoforms and epigenetic modulations.European journal of pharmacology · 2020Review
- How Can Drug Metabolism and Transporter Genetics Inform Psychotropic Prescribing?Frontiers in genetics · 2020Review
- Neonatal cytochrome P450 CYP3A7: A comprehensive review of its role in development, disease, and xenobiotic metabolism.Archives of biochemistry and biophysics · 2019Review
- Epigenetic Modifications of the Liver Tumor Cell Line HepG2 Increase Their Drug Metabolic Capacity.International journal of molecular sciences · 2019Article
- Regulation of cytochrome P450 expression by microRNAs and long noncoding RNAs: Epigenetic mechanisms in environmental toxicology and carcinogenesis.Journal of environmental science and health. Part C, Environmental carcinogenesis & ecotoxicology reviews · 2019Article
6 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
backgroundDNA methylation and histone deacetylation are epigenetic mechanisms that play major roles in eukaryotic gene regulation. We hypothesize that many genes in the human hepatoma cell line HepG2 are regulated by DNA methylation and histone deacetylation. Treatment with 5-aza-2'-deoxycytidine (5-aza-dC) to inhibit DNA methylation with and/or Trichostatin A (TSA) to inhibit histone deacetylation should allow us to identify genes that are regulated epigenetically in hepatoma cells.
results5-aza-dC had a much larger effect on gene expression in HepG2 cells than did TSA, as measured using Affymetrix HG-U133 Plus 2.0 microarrays. The expression of 1504 probe sets was affected by 5-aza-dC (at p < 0.01), 535 probe sets by TSA, and 1929 probe sets by the combination of 5-aza-dC and TSA. 5-aza-dC treatment turned on the expression of 211 probe sets that were not detectably expressed in its absence. Expression of imprinted genes regulated by DNA methylation, such as H19 and NNAT, was turned on or greatly increased in response to 5-aza-dC. Genes involved in liver processes such as xenobiotic metabolism (CYP3A4, CYP3A5, and CYP3A7) and steroid biosynthesis (CYP17A1 and CYP19A1), and genes encoding CCAAT element-binding proteins (C/EBPalpha, C/EBPbeta, and C/EBPgamma) were affected by 5-aza-dC or the combination. Many of the genes that fall within these groups are also expressed in the developing fetal liver and adult liver. Quantitative real-time RT-PCR assays confirmed selected gene expression changes seen in microarray analyses.
conclusionEpigenetics play a role in regulating the expression of several genes involved in essential liver processes such as xenobiotic metabolism and steroid biosynthesis in HepG2 cells. Many genes whose expression is normally silenced in these hepatoma cells were re-expressed by 5-aza-dC treatment. DNA methylation may be a factor in restricting the expression of fetal genes during liver development and in shutting down expression in hepatoma cells.
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