ArticleNature communications2019
Aberrant enhancer hypomethylation contributes to hepatic carcinogenesis through global transcriptional reprogramming.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 103 citations in OpenAlex.
- Targeting the C/EBPβ-PRAME-EZH2 complex modulates the Netrin-4/AKT axis to inhibit renal cancer tumorigenesis and metastasis.Cell death and differentiation · 2026Article
- Super-enhancer-associated lncRNA HDAC11-AS1 aggravates hepatocellular carcinoma progression by modulating HDAC11 and NUP210 expression via promoting super-enhancer activity.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- HOXA9 orchestrates EMT and metastasis in oral cancer via transcriptional activation of vimentin and β-catenin signaling.Cell death & disease · 2026Article
- Crosstalk BetweenCancers · 2026Review
- Review
- Deciphering the regulatory landscape of enhancer RNAs in health and disease.Signal transduction and targeted therapy · 2026Review
- New understanding of the molecular pathogenesis and therapeutic progress of hepatocellular carcinoma.Oncology reviews · 2026Review
- Physicochemical features of intrinsically disordered regions predict DNA-demethylation-promoting activity of transcription factors.Epigenetics & chromatin · 2025Article
- Genome-wide profiling of unmodified DNA using methyltransferase-directed tagging and enrichment.Cell reports methods · 2025Article
- Intra-tumoral epigenetic heterogeneity and aberrant molecular clocks in hepatocellular carcinoma.medRxiv : the preprint server for health sciences · 2025Article
- Super-enhancers orchestrate transcriptional dysregulation and metabolic reprogramming in uveal melanoma.Communications biology · 2025Article
- The epigenetic basis of hepatocellular carcinoma - mechanisms and potential directions for biomarkers and therapeutics.British journal of cancer · 2025Review
- Insight into the role of DNA methylation in prognosis and treatment response prediction of gastrointestinal cancers.Epigenomics · 2025Review
- Exploring methylation signatures for high de novo recurrence risk in hepatocellular carcinoma.Clinical and molecular hepatology · 2025Article
- Unraveling the intricate molecular landscape and potential biomarkers in lung adenocarcinoma through integrative epigenomic and transcriptomic profiling.Scientific reports · 2025Article
- Super-enhancer DNA methylation in cancer: the mechanism of action and therapeutic directions.Frontiers in oncology · 2025Review
- Super-enhancers in immune system regulation: mechanisms, pathological reprogramming, and therapeutic opportunities.Frontiers in immunology · 2025Review
- Active enhancers: recent research advances and insights into disease.Biology direct · 2024Review
- Comprehensive review and updated analysis of DNA methylation in hepatocellular carcinoma: From basic research to clinical application.Clinical and translational medicine · 2024Review
- Enhancer demethylation-regulated gene score identified molecular subtypes, inspiring immunotherapy or CDK4/6 inhibitor therapy in oesophageal squamous cell carcinoma.EBioMedicine · 2024Article
11 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
30 authors at 6 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatocellular carcinomas (HCC) exhibit distinct promoter hypermethylation patterns, but the epigenetic regulation and function of transcriptional enhancers remain unclear. Here, our affinity- and bisulfite-based whole-genome sequencing analyses reveal global enhancer hypomethylation in human HCCs. Integrative epigenomic characterization further pinpoints a recurrent hypomethylated enhancer of CCAAT/enhancer-binding protein-beta (C/EBPβ) which correlates with C/EBPβ over-expression and poorer prognosis of patients. Demethylation of C/EBPβ enhancer reactivates a self-reinforcing enhancer-target loop via direct transcriptional up-regulation of enhancer RNA. Conversely, deletion of this enhancer via CRISPR/Cas9 reduces C/EBPβ expression and its genome-wide co-occupancy with BRD4 at H3K27ac-marked enhancers and super-enhancers, leading to drastic suppression of driver oncogenes and HCC tumorigenicity. Hepatitis B X protein transgenic mouse model of HCC recapitulates this paradigm, as C/ebpβ enhancer hypomethylation associates with oncogenic activation in early tumorigenesis. These results support a causal link between aberrant enhancer hypomethylation and C/EBPβ over-expression, thereby contributing to hepatocarcinogenesis through global transcriptional reprogramming.
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Registered trials
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.