Functional studies demonstrated that this loss of state identity coincides with decreased self-renewal and invasion in GSCs and delayed tumor initiation and progression in a mouse GBM model.<h4>Conclusion</h4>Collectively, our results establish EP300 as a key regulator of IR state identity in GSCs and provide a mechanistic basis for therapeutic targeting of aggressive cellular states in GBM. This evidence concerns the gene EP300 and glioblastoma.