ArticleCell death & disease2019
EZH2, JMJD3, and UTX epigenetically regulate hepatic plasticity inducing retro-differentiation and proliferation of liver cells.
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 31 citations in OpenAlex.
- JMJD3-mediated HADH demethylation orchestrates hepatocyte maturation through fatty acid β-oxidation-dependent histone acetylation.Experimental & molecular medicine · 2026Article
- Sex-specific KDM6A-HNF4A-CREBH network controls lipoprotein cholesterol metabolism and atherosclerosis via epigenetic reprograming of hepatocytes.Nature communications · 2026Article
- The JMJD family histone demethylases: structure, mechanism of action, diseases and therapeutic targets.Molecular biomedicine · 2026Review
- Roles of Kdm6a and Kdm6b in Regulation of Mammalian Neural Regeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Suppression of the H3K27me3 demethylase disrupts diapause formation in mosquito Culex pipiens.Insect biochemistry and molecular biology · 2025Article
- Overexpression ofBioMed research international · 2025Article
- Role and potential therapeutic value of histone methyltransferases in drug resistance mechanisms in lung cancer.Frontiers in oncology · 2024Review
- Article
- H3K27me3 Immunohistochemical Loss Predicts Lower Response to Neo-Adjuvant Chemo-Radiotherapy in Rectal Carcinoma.Biomedicines · 2022Article
- Emerging roles of JMJD3 in cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2022Review
- Article
- P53 suppresses the progression of hepatocellular carcinoma via miR-15a by decreasing OGT expression and EZH2 stabilization.Journal of cellular and molecular medicine · 2021Article
- Deregulation of Transcriptional Enhancers in Cancer.Cancers · 2021Review
- Role of Nitric Oxide in Gene Expression Regulation during Cancer: Epigenetic Modifications and Non-Coding RNAs.International journal of molecular sciences · 2021Review
- The Functions of the Demethylase JMJD3 in Cancer.International journal of molecular sciences · 2021Review
- Histone H3K27 methyltransferase EZH2 and demethylase JMJD3 regulate hepatic stellate cells activation and liver fibrosis.Theranostics · 2021Article
- Epigenetic Control of Autophagy Related Genes Transcription in Pulpitis via JMJD3.Frontiers in cell and developmental biology · 2021Article
- Specific Protein 1 and p53 Interplay Modulates the Expression of the KCTD-Containing Cullin3 Adaptor Suppressor of Hedgehog 2.Frontiers in cell and developmental biology · 2021Article
- Determination of long non-coding RNAs associated with EZH2 in neuroblastoma by RIP-seq, RNA-seq and ChIP-seq.Oncology letters · 2020Article
- SETDB1 promotes the progression of colorectal cancer via epigenetically silencing p21 expression.Cell death & disease · 2020Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Modification of histones by lysine methylation plays a role in many biological processes, and it is dynamically regulated by several histone methyltransferases and demethylases. The polycomb repressive complex contains the H3K27 methyltransferase EZH2 and controls dimethylation and trimethylation of H3K27 (H3K27me2/3), which trigger gene suppression. JMJD3 and UTX have been identified as H3K27 demethylases that catalyze the demethylation of H3K27me2/3, which in turns lead to gene transcriptional activation. EZH2, JMJD3 and UTX have been extensively studied for their involvement in development, immune system, neurodegenerative disease, and cancer. However, their role in molecular mechanisms underlying the differentiation process of hepatic cells is yet to be elucidated. Here, we show that EZH2 methyltransferase and JMJD3/UTX demethylases were deregulated during hepatic differentiation of human HepaRG cells resulting in a strong reduction of H3K27 methylation levels. Inhibition of JMJD3 and UTX H3K27 demethylase activity by GSK-J4 epi-drug reverted phenotype of HepaRG DMSO-differentiated cells and human primary hepatocytes, drastically decreasing expression of hepatic markers and inducing cell proliferation. In parallel, inhibition of EZH2 H3K27me3 activity by GSK-126 epi-drug induced upregulation of hepatic markers and downregulated the expression of cell cycle inhibitor genes. To conclude, we demonstrated that modulation of H3K27 methylation by inhibiting methyl-transferase and dimethyl-transferase activity influences the differentiation status of hepatic cells, identifying a possible new role of EZH2, JMJD3 and UTX epi-drugs to modulate hepatic cell plasticity.
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