GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE269nnn/GSE269909/primaryOK200TranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE269909GEOGSEfalseDivergent medulloblastoma chromatin states disclose KDM2B as a selective dependency [RNA-Seq]Medulloblastoma (MB) is a biologically heterogeneous childhood cerebellar tumor harboring frequent chromatin-modifying gene alterations. How these alterations promote transcriptional programs governing malignancy remains poorly defined. To address this knowledge gap, we evaluated chromatin states across MB subgroups by multi-modal integration of histone modifications with mutational, DNA methylation, and transcriptomic profiles. A bivalent/poised enhancer (EnhBiv) state was specifically enriched at the promoters of neurodevelopmental genes in Groups 3 and 4-MB. Integrative bioinformatics coupled with chromatin occupancy studies identified aberrant KDM2B binding at EnhBiv-enriched promoters. CRISPR-mediated knockout or acute protein degradation of KDM2B selectively suppressed the growth of MB models in vitro and in vivo. Mechanistically, KDM2B promotes sequential recruitment of Polycomb repressive complexes (PRC1/PRC2) and EnhBiv chromatin, thereby repressing neuronal differentiation programs. Collectively, we provide foundational insights into an epigenetic basis of MB, nominating KDM2B as a selective dependency in high-risk subgroups that warrants consideration as a candidate therapeutic target.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 sapiens