EZHIP boosts neuronal-like synaptic gene programs and depresses polyamine metabolism
Rattachement africain : ca, us. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
It is currently understood that the characteristic loss of the repressive histone mark H3K27me3 in PFA ependymoma and diffuse midline glioma (DMG) are caused by complementary mechanisms mediated by EZHIP and the oncohistone H3K27M, respectively. To support the complementarity of these mechanisms, rare H3K27M-negative DMGs express EZHIP. Interestingly, EZHIP is one of the few genes recurrently mutated in PFA. The significance of EZHIP mutations in PFA, and whether EZHIP has wider functions in addition to repression of H3K27me3 deposition, are not known. Here, we investigated the mutational landscape of EZHIP in pediatric brain tumors. We found that EZHIP mutations occur not only in PFA, but also in rare medulloblastoma and pediatric high-grade glioma (HGG), including in H3K27-positive DMG. Contrary to current expectations, we show that mutant EZHIP is expressed in H3K27M-positive DMG. All the EZHIP-mutated HGG cases also have EGFR mutations. Further, we pursued better understanding of the function of EZHIP by expressing it in human-derived neural models. Our transcriptomic analyses indicate that EZHIP expression potentiates neuronal-like gene programs associated with synaptic function. Metabolomics data indicate that EZHIP leads to repression of methionine and polyamine metabolism, suggesting links between metabolic and epigenetic changes that are observed in PFA. Collectively, our results expand the repertoire of tumor types known to harbor EZHIP mutations and shed light on EZHIP-dependent metabolic and transcriptional programs in relevant neural models.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- EZHIP boosts neuronal-like synaptic gene programs and depresses polyamine metabolism
- Date Crossref
- 07/11/2025
- Éditeur
- Springer Science and Business Media LLC
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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University of Calgary pays non établi dans la noticeUniversité ou école supérieure
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Alberta Children's Hospital pays non établi dans la noticeÉtablissement de santé
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Baylor College of Medicine Department of Pediatrics pays non établi dans la noticeUniversité ou école supérieure
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Texas Children's Hospital Cancer and Hematology Center pays non établi dans la noticeOrganisme public
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Children's Cancer Center pays non établi dans la noticeOrganisation à but non lucratif
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University of Pittsburgh Department of Neurological Surgery pays non établi dans la noticeUniversité ou école supérieure
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Neurological Surgery pays non établi dans la noticeÉtablissement de santé
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Cumming School of Medicine pays non établi dans la noticeUniversité ou école supérieure
University of Calgary, Alberta Children's Hospital et Department of Pediatrics — Baylor College of Medicine, avec 5 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.