ArticleCell death and differentiation2022
E2F and STAT3 provide transcriptional synergy for histone variant H2AZ activation to sustain glioblastoma chromatin accessibility and tumorigenicity.
Article in Cell death and differentiation, 2022. 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, 33 citations in OpenAlex.
- E2F3a transcription factor mediates behavioral, cellular, and DNA-protein regulation of cocaine reward in the nucleus accumbens.Molecular psychiatry · 2026Article
- Histone Variant H2A.Z2 Hyper-Transcription Induced by E2F1 Accelerates Lung Adenocarcinoma Progression via the JAK-STAT Signaling Pathway.Thoracic cancer · 2026Article
- Genome-wide CRISPR screen identifies a cytokine-enhancer circuit driving HIF-2α activation in renal cancer.The Journal of clinical investigation · 2026Article
- Skin Epidermal Progenitor Maintenance by the SRCAP-H2A.Z Axis Downstream to Extracellular Signal-Regulated Kinase and mTOR Signaling.The Journal of investigative dermatology · 2026Article
- The therapeutic effect and specific mechanism involved active Chinese medicine component biochaninA in glioma.Frontiers in immunology · 2026Article
- Prognostic and immunotherapeutic response prediction in hepatocellular carcinoma: role of non-histone acetylation/deacetylation scoring.Discover oncology · 2025Article
- CRISPR-Cas9 screening identifies a gene signature predictive of prognosis in glioblastoma.Scientific reports · 2025Article
- Article
- A human-specific, concerted repression of microcephaly genes contributes to radiation-induced growth defects in cortical organoids.iScience · 2025Article
- E2F1 activates breast stromal fibroblasts and promotes their paracrine pro-carcinogenic effects.Scientific reports · 2025Article
- Chromatin accessibility: biological functions, molecular mechanisms and therapeutic application.Signal transduction and targeted therapy · 2024Review
- Histone demethylase KDM2A recruits HCFC1 and E2F1 to orchestrate male germ cell meiotic entry and progression.The EMBO journal · 2024Article
- Navigating glioblastoma complexity: the interplay of neurotransmitters and chromatin.Molecular biology reports · 2024Review
- METTL8 links mt-tRNA mCell death & disease · 2024Article
- Inhibition of high level E2F in a RB1 proficient MYCN overexpressing chicken retinoblastoma model normalizes neoplastic behaviour.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- POLR2J expression promotes glioblastoma malignancy by regulating oxidative stress and the STAT3 signaling pathway.American journal of cancer research · 2024Article
- Biological underpinnings of radiomic magnetic resonance imaging phenotypes for risk stratification in IDH wild-type glioblastoma.Journal of translational medicine · 2023Article
- CAMK2D serves as a molecular scaffold for RNF8-MAD2 complex to induce mitotic checkpoint in glioma.Cell death and differentiation · 2023Article
- Evolving Diagnostic and Treatment Strategies for Pediatric CNS Tumors: The Impact of Lipid Metabolism.Biomedicines · 2023Review
- Article
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The histone variant H2AZ is overexpressed in diverse cancer types where it facilitates the accessibility of transcriptional regulators to the promoters of cell cycle genes. However, the molecular basis for its dysregulation in cancer remains unknown. Here, we report that glioblastomas (GBM) and glioma stem cells (GSCs) preferentially overexpress H2AZ for their proliferation, stemness and tumorigenicity. Chromatin accessibility analysis of H2AZ2 depleted GSC revealed that E2F1 occupies the enhancer region within H2AZ2 gene promoter, thereby activating H2AZ2 transcription. Exploration of other H2AZ2 transcriptional activators using a customized "anti-H2AZ2" query signature for connectivity map analysis identified STAT3. Co-targeting E2F and STAT3 synergistically reduced the levels of H2AZ, histone 3 lysine 27 acetylation (H3K27ac) and cell cycle gene transcription, indicating that E2F1 and STAT3 synergize to activate H2AZ gene transcription in GSCs. Remarkably, an E2F/STAT3 inhibitor combination durably suppresses GSC tumorigenicity in an orthotopic GBM xenograft model. In glioma patients, high STAT3 signaling is associated with high E2F1 and H2AZ2 expression. Thus, GBM has uniquely opted the use of E2F1- and STAT3-containing "enhanceosomes" that integrate multiple signaling pathways to achieve H2AZ gene activation, supporting a translational path for the E2F/STAT3 inhibitor combination to be applied in GBM treatment.
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