RNA-seq, CUT&RUN, invasion assays, sphere-forming assays, and a mouse GBM model were used to characterize the phenotypic consequences of EP300 perturbation.<h4>Results</h4>We found that perturbation of the histone acetyltransferase EP300 led to decreased CD44 cell surface expression, and loss of IR transcriptional state identity through dysregulation of the epigenome. Here, CD44 is linked to glioblastoma.