{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Histone H3 variants, including those encoded by the canonical gene cluster (such as HIST1H3C) and the replication‐independent variant H3.3, are key components of nucleosomal chromatin that regulate gene expression, genome stability, and cell identity. In normal cells, these histones act as structural platforms for epigenetic modifications that govern chromatin accessibility and transcription. For example, they are deposited through dedicated chaperone systems – with H3.3 being loaded by the DAXX/ATRX complex and CENP‑A (a specialized H3 variant at centromeres) assembled via HJURP – thus ensuring proper chromatin configuration during transcription, replication, and DNA repair (4,5,12,26)."}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the setting of pediatric high‐grade gliomas and diffuse intrinsic pontine gliomas (DIPG), somatic missense mutations—most notably at lysine 27 (K27M) and glycine 34—have been identified in both H3.3 (H3F3A/H3F3B) and canonical H3 genes (including those in the HIST1H3 cluster, of which HIST1H3C is a member) (1,2,6,7,16,36). These mutations disturb the normal pattern of post‐translational modifications such as H3K27 trimethylation, triggering a global epigenetic reprogramming that defines distinct molecular subgroups and is tightly linked to aggressive tumor behavior and poor clinical outcome (1,6,16,36)."}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond their role in pediatric gliomagenesis, histone H3 variants are also implicated in other oncogenic processes through their influence on transcriptional elongation, chromatin assembly, and even alternative RNA splicing, thereby contributing to tumor cell growth and metastasis (13,14,21,23). Alterations in the methylation state of histone H3 genes, including aberrant promoter methylation of HIST1H3C, may serve not only as critical effectors of oncogenic transformation but also as prognostic biomarkers for risk stratification in tumors such as neuroblastoma (39).\n\n "}, {"type": "rg", "children": []}]}]}