GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE270nnn/GSE270125/primary200OKOtherHomo sapiens Genome binding/occupancy profiling by high throughput sequencingOtherhttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE270125GEOGSEfalseDivergent medulloblastoma chromatin states disclose KDM2B as a selective dependency [CUT&Run]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