ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2015
The methyltransferases enhancer of zeste homolog (EZH) 1 and EZH2 control hepatocyte homeostasis and regeneration.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 56 citations in OpenAlex.
- Hepatocyte Embryonic Ectoderm Development (Eed) Deficiency Causes Liver Injury, Fibrosis, and Impacts Liver Regeneration.bioRxiv : the preprint server for biology · 2026Article
- Noncanonical EZH2 activity cooperates with FOXM1 to drive tumorigenesis and advanced progression in HCC.Clinical and molecular hepatology · 2026Article
- Derepression of the epithelial transcription factor GRHL2 promotes direct hepatocyte-to-cholangiocyte transdifferentiation.PLoS biology · 2025Article
- EZH1 Inhibition attenuates apoptosis and promotes regeneration for liver repair in acute liver failure.BMC gastroenterology · 2025Article
- Enolase and 16.5-kDa Tegument-Associated Protein inJournal of extracellular biology · 2025Article
- Cell atlas of CClZoological research · 2023Article
- The Contribution of the Zebrafish Model to the Understanding of Polycomb Repression in Vertebrates.International journal of molecular sciences · 2023Review
- Fibrosis-the tale of H3K27 histone methyltransferases and demethylases.Frontiers in cell and developmental biology · 2023Review
- Epigenetic controls of Sonic hedgehog guarantee fidelity of epithelial adult stem cells trajectory in regeneration.Science advances · 2022Article
- Screening differential circular RNA expression profiles reveals the regulatory role of circMARS in anti-tuberculosis drug-induced liver injury.Journal of cellular and molecular medicine · 2022Article
- EZH1/2 inhibition augments the anti-tumor effects of sorafenib in hepatocellular carcinoma.Scientific reports · 2021Article
- DeepProg: an ensemble of deep-learning and machine-learning models for prognosis prediction using multi-omics data.Genome medicine · 2021Article
- PRC2 insufficiency causes p53-dependent dyserythropoiesis in myelodysplastic syndrome.Leukemia · 2021Article
- Epigenetic Regulation of Cell-Fate Changes That Determine Adult Liver Regeneration After Injury.Frontiers in cell and developmental biology · 2021Review
- EZH2 as a Potential Target for NAFLD Therapy.International journal of molecular sciences · 2020Review
- The polycomb proteins EZH1 and EZH2 co-regulate chromatin accessibility and nephron progenitor cell lifespan in mice.The Journal of biological chemistry · 2020Article
- Sex-biased genetic programs in liver metabolism and liver fibrosis are controlled by EZH1 and EZH2.PLoS genetics · 2020Article
- Proteasomal Degradation of Enhancer of Zeste Homologue 2 in Cholangiocytes Promotes Biliary Fibrosis.Hepatology (Baltimore, Md.) · 2019Article
- Maintenance of CTCF- and Transcription Factor-Mediated Interactions from the Gametes to the Early Mouse Embryo.Molecular cell · 2019Article
- HCV-Induced Epigenetic Changes Associated With Liver Cancer Risk Persist After Sustained Virologic Response.Gastroenterology · 2019Article
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
To investigate the role of enhancer of zeste homolog (EZH) 1 and EZH2 in liver homeostasis, mice were generated that carried Ezh1(-/-) and EZH2(fl/fl) alleles and an Alb-Cre transgene. Only the combined loss of EZH1 and EZH2 in mouse hepatocytes caused a depletion of global trimethylation on Lys 27 of histone H3 (H3K27me3) marks and the specific loss of over ∼1900 genes at 3 mo of age. Ezh1(-/-),Ezh2(fl/fl)Alb-Cre mice exhibited progressive liver abnormalities manifested by the development of regenerative nodules and concomitant periportal fibrosis, inflammatory infiltration, and activation of A6-positive hepatic progenitor cells at 8 mo of age. In response to chronic treatment with carbon tetrachloride, all experimental mice, but none of the controls (n = 27 each), showed increased hepatic degeneration associated with liver dysfunction and reduced ability to proliferate. After two-thirds partial hepatectomy, mutant mice (n = 5) displayed increased liver injury and a blunted regenerative response. Genome-wide analyses at 3 mo of age identified 51 genes that had lost H3K27me3 marks, and their expression was significantly increased. These genes were involved in regulation of cell survival, fibrosis, and proliferation. H3K27me3 levels and liver physiology were unaffected in mice lacking either EZH1 globally or EZH2 specifically in hepatocytes. This work demonstrates a critical redundancy of EZH1 and EZH2 in maintaining hepatic homeostasis and regeneration.
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