ArticleGastroenterology2019
Polycomb Repressive Complex 2 Proteins EZH1 and EZH2 Regulate Timing of Postnatal Hepatocyte Maturation and Fibrosis by Repressing Genes With Euchromatic Promoters in Mice.
Article in Gastroenterology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 33 citations in OpenAlex.
- Epigenetic regulation of kidney development.Nature reviews. Nephrology · 2026Review
- JMJD3-mediated HADH demethylation orchestrates hepatocyte maturation through fatty acid β-oxidation-dependent histone acetylation.Experimental & molecular medicine · 2026Article
- Hepatocyte Embryonic Ectoderm Development (Eed) Deficiency Causes Liver Injury, Fibrosis, and Impacts Liver Regeneration.bioRxiv : the preprint server for biology · 2026Article
- PAR3-mediated coordination of hepatocyte proliferation, maturation, and architecture in liver development and regeneration.Nature communications · 2026Article
- Hepatocyte-targeted Bap1 reduction in the liver primes an inflammatory transcriptional response.G3 (Bethesda, Md.) · 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
- Present and Future Perspectives in the Treatment of Liver Fibrosis.Pharmaceuticals (Basel, Switzerland) · 2025Review
- EZH1 deficiency promotes ferroptosis resistance by activating NRF2 in sepsis-associated liver injury.Clinical epigenetics · 2025Article
- EZH2 deletion does not affect acinar regeneration but restricts progression to pancreatic cancer in mice.JCI insight · 2024Article
- Epigenetic control and manipulation of neuronal maturation timing.Current opinion in genetics & development · 2024Review
- Article
- Disrupting Poly(ADP-ribosyl)ating Pathway Creates Premalignant Conditions in Mammalian Liver.International journal of molecular sciences · 2023Article
- Found in translation-Fibrosis in metabolic dysfunction-associated steatohepatitis (MASH).Science translational medicine · 2023Review
- Fibrosis-the tale of H3K27 histone methyltransferases and demethylases.Frontiers in cell and developmental biology · 2023Review
- An EZH2-dependent transcriptional complex promotes aberrant epithelial remodelling after injury.EMBO reports · 2021Article
- Epigenetic Modulation of Radiation-Induced Diacylglycerol Kinase Alpha Expression Prevents Pro-Fibrotic Fibroblast Response.Cancers · 2021Article
- EZH2 as a Potential Target for NAFLD Therapy.International journal of molecular sciences · 2020Review
- Sex-biased genetic programs in liver metabolism and liver fibrosis are controlled by EZH1 and EZH2.PLoS genetics · 2020Article
- Understanding Dietary Intervention-Mediated Epigenetic Modifications in Metabolic Diseases.Frontiers in genetics · 2020Review
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsLittle is known about mechanisms that underlie postnatal hepatocyte maturation and fibrosis at the chromatin level. We investigated the transcription of genes involved in maturation and fibrosis in postnatal hepatocytes of mice, focusing on the chromatin compaction the roles of the Polycomb repressive complex 2 histone methyltransferases EZH1 and EZH2.
methodsHepatocytes were isolated from mixed background C57BL/6J-C3H mice, as well as mice with liver-specific disruption of Ezh1 and/or Ezh2, at postnatal day 14 and 2 months after birth. Liver tissues were collected and analyzed by RNA sequencing, H3K27me3 chromatin immunoprecipitation sequencing, and sonication-resistant heterochromatin sequencing (a method to map heterochromatin and euchromatin). Liver damage was characterized by histologic analysis.
resultsWe found more than 3000 genes differentially expressed in hepatocytes during liver maturation from postnatal day 14 to month 2 after birth. Disruption of Ezh1 and Ezh2 in livers caused perinatal hepatocytes to differentiate prematurely and to express genes at postnatal day 14 that would normally be induced by month 2 and differentiate prematurely. Loss of Ezh1 and Ezh2 also resulted in liver fibrosis. Genes with H3K27me3-postive and H3K4me3-positive euchromatic promoters were prematurely induced in hepatocytes with loss of Ezh1 and Ezh2-these genes included those that regulate hepatocyte maturation, fibrosis, and genes not specifically associated with the liver lineage.
conclusionsThe Polycomb repressive complex 2 proteins EZH1 and EZH2 regulate genes that control hepatocyte maturation and fibrogenesis and genes not specifically associated with the liver lineage by acting at euchromatic promoter regions. EZH1 and EZH2 thereby promote liver homeostasis and prevent liver damage. Strategies to manipulate Polycomb proteins might be used to improve hepatocyte derivation protocols or developed for treatment of patients with liver fibrosis.
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