Divergent medulloblastoma chromatin states disclose KDM2B as a selective dependency [CUT&Run]

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.