ArticlePLoS biology2024
MYCN drives oncogenesis by cooperating with the histone methyltransferase G9a and the WDR5 adaptor to orchestrate global gene transcription.
Article in PLoS biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
9 citing papers in PubMed, 8 citations in OpenAlex.
- Targeting MYC-Driven Cancers: From Oncogenic Addiction to Therapeutic Vulnerability.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Decoding WDR5-Mediated Interactions in Gliomas: Implications for Targeted Therapy.Medicinal research reviews · 2026Review
- MYCN-driven metabolic remodelling of the tumour microenvironment in neuroblastoma: implications for stromal biology and CAF heterogeneity.Cancer metastasis reviews · 2026Review
- Targeting the MYCN interaction network in neuroblastoma.Bioscience reports · 2026Review
- Cohesin Loading Factor NIPBL Is Essential for MYCN Expression and MYCN-Driven Oncogenic Transcription in Neuroblastoma.Cancers · 2025Article
- ONC201 exerts oncogenic effects beyond its mitochondria-disturbing role in neuroblastoma subsets.Journal of molecular medicine (Berlin, Germany) · 2025Article
- MYCN and KAT2A form a feedforward loop to drive an oncogenic transcriptional program in neuroblastoma.Oncogenesis · 2025Article
- Molecular principles underlying aggressive cancers.Signal transduction and targeted therapy · 2025Review
- Molecular regulation and therapeutic targeting ofFrontiers in cell and developmental biology · 2025Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
MYCN activates canonical MYC targets involved in ribosome biogenesis, protein synthesis, and represses neuronal differentiation genes to drive oncogenesis in neuroblastoma (NB). How MYCN orchestrates global gene expression remains incompletely understood. Our study finds that MYCN binds promoters to up-regulate canonical MYC targets but binds to both enhancers and promoters to repress differentiation genes. MYCN binding also increases H3K4me3 and H3K27ac on canonical MYC target promoters and decreases H3K27ac on neuronal differentiation gene enhancers and promoters. WDR5 facilitates MYCN promoter binding to activate canonical MYC target genes, whereas MYCN recruits G9a to enhancers to repress neuronal differentiation genes. Targeting both MYCN's active and repressive transcriptional activities using both WDR5 and G9a inhibitors synergistically suppresses NB growth. We demonstrate that MYCN cooperates with WDR5 and G9a to orchestrate global gene transcription. The targeting of both these cofactors is a novel therapeutic strategy to indirectly target the oncogenic activity of MYCN.
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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.