EZH2 (PRC2) trimethylates H3K27 → PRC1 recruitment → chromatin compaction → transcriptional silencing.
Elegant at the mechanistic level. Consequential at the organismal level — elevated EZH2 activity shortens lifespan in model organisms, likely via progressive silencing of stress-response loci.
The SET domain may be one of the most underrated targets in aging biology.
#EZH2 #PRC2 #Epigenetics #AgingBiology #H3K27me3 #ChromatinRemodeling #Longevity
Un enzima chiamato EZH2 decide quali cellule tumorali diventeranno metastasi. Non modifica il DNA direttamente: lo avvolge, silenziando i geni che mantengono l'ordine nella divisione cellulare. Il 5% delle cellule del tumore triplo negativo usa questo meccanismo per viaggiare. La buona notizia? Esistono farmaci che bloccano EZH2 e sono già stati approvati.
https://www.futuroprossimo.it/2025/10/ezh2-trovato-linterruttore-delle-metastasi/
Seung Kim, Frederick Dick et al show that resting #Bcells are uniquely sensitive to #EZH2 #polycomb complex inhibition, which activates expression of repetitive genomic elements and subsequent #innateimmune receptor signaling in a form of viral mimicry
"These data identify developmental lineage as a key determinant of sensitivity to anti-GD2 based immunotherapies and credential #EZH2 inhibitors for clinical testing in combination with anti-GD2 antibody to enhance outcomes for children with #neuroblastoma".
An article that I had missed, by Mabe et al., linking #mesenchymal #tumour cell state, #GD2 expression, #ST8SIA1 expression, and #immunotherapy #TherapyResistance.
https://www.nature.com/articles/s43018-022-00405-x
Sadly, not open access.
Mabe et al. find that GD2 levels correlate with lineage plasticity in neuroblastoma and identify ST8SIA1 as the key enzyme in GD2 synthesis. EZH2 inhibition in mesenchymal neuroblastoma cells elevates ST8SIA1, synergizing with anti-GD2 antibodies.
Alice Frolov
Futuro Prossimo 
The EMBO Journal
Arjan Boltjes
CavalliLab