DIPG accounts for 10% of all childhood central nervous system tumors, are highly aggressive and difficult to treat brain tumors at brainstem. ~ 80% of DIPG patients harbor mutations on lysine 27 of histone 3 which colocalizes with bromodomain proteins to sites of active transcription. p300 is a multi-domain enhancer protein which includes bromo domain (BrD) and PHD domain, is expressed in 80% of gliomas. Based on our findings, bromodomain inhibitors (BrDi) have been suggested as a potential therapeutic target for DIPG and have shown antiproliferative activity in vitro. We therefore hypothesize that p300 -BrD inhibition is a potential therapeutic strategy that must be urgently explored in DIPG.