Histone H3.3 lysine 27-to-methionine mutant epitope (H3.3 K27M)

The **histone H3.3 lysine 27-to-methionine mutant epitope** (H3.3 K27M) refers to a specific mutation in the histone variant H3.3, in which lysine at position 27 is replaced by methionine. This mutation is most notably found in pediatric high-grade gliomas, especially diffuse midline glioma (DMG)/diffuse intrinsic pontine glioma (DIPG), and is considered oncogenic. The K27M alteration leads to global loss of H3K27 trimethylation (H3K27me3) by dominantly inhibiting the histone methyltransferase EZH2 (component of Polycomb repressive complex 2), thereby dysregulating gene silencing and promoting aberrant gene expression[1][2][3][4]. This mutant epitope both marks tumor cells for molecular pathology diagnosis and represents a unique neo-epitope for targeted therapies under clinical investigation. Its presence is associated with major changes in the chromatin landscape, alterations in enhancer/super-enhancer activity related to neurogenesis and proliferation programs, and defects in chromatin remodeling, as well as disruption of nuclear body organization in the affected cells[3][4].

Other names

H3F3A K27MH3.3K27MH3-3A K27MH3K27M mutantK27M mutant

Epigenetic reprogramming/via inhibition or alteration of histone methylation (notably H3K27me3) - Inhibition of mutant histone function or restoration of repressive chromatin marks