ArticleNature communications2018
The histone demethylase Phf2 acts as a molecular checkpoint to prevent NAFLD progression during obesity.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 87 citations in OpenAlex.
- Effects of TNF-α in Human Precision-Cut Liver Slices and its Implications for Metabolic Dysfunction-Associated Steatohepatitis Progression.Inflammation · 2026Article
- Hp1bp3 loss links chromatin reorganization to metabolic vulnerability in glioma.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The role of hepatocyte epigenetics in the pathogenesis of metabolic dysfunction-associated steatotic liver disease.Communications medicine · 2026Review
- Article
- Histone demethylase PHF2 regulates inflammatory genes in Alzheimer's disease.Molecular psychiatry · 2026Article
- Histone Methylation: A Pivotal Epigenetic Driver of the Malignant Transformation of MASLD-HCC.Journal of hepatocellular carcinoma · 2026Review
- Epigenetic Changes Associated With Obesity-related Metabolic Comorbidities.Journal of the Endocrine Society · 2025Review
- Comprehensive Transcriptomic and Epigenomic Insights into Environmental Toxicant Exposures: The TaRGET II Resource.bioRxiv : the preprint server for biology · 2025Article
- GOLM1 promotes cholesterol gallstone formation via ABCG5-mediated cholesterol efflux in metabolic dysfunction-associated steatohepatitis livers.Clinical and molecular hepatology · 2025Article
- Comprehensive understanding of context-specific functions of PHF2 in lipid metabolic tissues.Scientific reports · 2025Article
- Mechanism of valproic acid-induced hepatic steatosis via enhancing NRF2-FATP2-mediated fatty acid uptake.Theranostics · 2025Article
- ChREBP-mediated up-regulation of Them1 coordinates thermogenesis with glycolysis and lipogenesis in response to chronic stress.Science signaling · 2024Article
- PHF2-mediated H3K9me balance orchestrates heterochromatin stability and neural progenitor proliferation.EMBO reports · 2024Article
- Unraveling the relationship between histone methylation and nonalcoholic fatty liver disease.World journal of hepatology · 2024Review
- The transcription factor ChREBP Orchestrates liver carcinogenesis by coordinating the PI3K/AKT signaling and cancer metabolism.Nature communications · 2024Article
- PHF2 regulates sarcomeric gene transcription in myogenesis.PloS one · 2024Article
- Histone methylation: at the crossroad between circadian rhythms in transcription and metabolism.Frontiers in genetics · 2024Review
- Recent developments in catalysis and inhibition of the Jumonji histone demethylases.Current opinion in structural biology · 2023Review
- Comprehensive analysis of epigenetic and epitranscriptomic genes' expression in human NAFLD.Journal of physiology and biochemistry · 2023Article
- Palmitoylation-driven PHF2 ubiquitination remodels lipid metabolism through the SREBP1c axis in hepatocellular carcinoma.Nature communications · 2023Article
1 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 7 institutions in 2 countries.
Funding
Abstract
Aberrant histone methylation profile is reported to correlate with the development and progression of NAFLD during obesity. However, the identification of specific epigenetic modifiers involved in this process remains poorly understood. Here, we identify the histone demethylase Plant Homeodomain Finger 2 (Phf2) as a new transcriptional co-activator of the transcription factor Carbohydrate Responsive Element Binding Protein (ChREBP). By specifically erasing H3K9me2 methyl-marks on the promoter of ChREBP-regulated genes, Phf2 facilitates incorporation of metabolic precursors into mono-unsaturated fatty acids, leading to hepatosteatosis development in the absence of inflammation and insulin resistance. Moreover, the Phf2-mediated activation of the transcription factor NF-E2-related factor 2 (Nrf2) further reroutes glucose fluxes toward the pentose phosphate pathway and glutathione biosynthesis, protecting the liver from oxidative stress and fibrogenesis in response to diet-induced obesity. Overall, our findings establish a downstream epigenetic checkpoint, whereby Phf2, through facilitating H3K9me2 demethylation at specific gene promoters, protects liver from the pathogenesis progression of NAFLD.
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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.