Polycomb-mediated repression of EphrinA5 promotes growth and invasion of glioblastoma

Glioblastoma (GBM) is the most common and most aggressive intrinsic brain tumour in adults. Integrated transcriptomic and epigenomic analyses of glioblastoma initiating cells (GIC) in a mouse model uncovered a novel epigenetic regulation of EfnA5. In this model, Bmi1 enhances H3K27me3 at the EfnA5 locus and reinforces repression of selected target genes in a cellular context dependent fashion. EfnA5 mediate Bmi1-dependent proliferation and invasion in vitro and tumour formation in an allograft model. Importantly, we show that this novel Polycomb feed-forward loop is also active in human GIC and we provide preclinical evidence of druggability of EFNA5 in GBM xenografts overexpressing BMI1. H3K27me3-ChIPSeq: 1 Control NSC, 1 Bmi1over NSC, 1 GIC. RNASeq: 2 replicas of control NSC, 2 replicas of Bmi1over NSC, 2 replicas of GIC.