EZH2 inhibition in glioblastoma stem cells is associated with increased expression of neuronal genes and the neuronal developmental regulators ZIC2, ZNF423 and MAFB

Here we use two GBM stem cell lines, representing the classical/pro-neural and mesenchymal GBM subtypes, to investigate the effects of three different EZH2 inhibitors on GBM stem cell survival and gene expression: EPZ6438, GSK343 and UNC1999. RNA-seq analysis revealed that all three EZH2 inhibitors led to increased expression of genes related to neurogenesis and/or neuronal structure in both GBM stem cell lines. Chromatin immunoprecipitation (ChIP-Seq) was used to identify potential direct targets of the histone methylation activity of EZH2 that might be driving the increase in neuronal gene expression. Overall design: Two glioblastoma stem cell lines were treated with various EZH2 inhibitors. RNAseq and ChIP-seq were performed in order to investigate the molecular changes.