CRISPR-based synthetic lethal screening has identified the acetyltransferases p300 and CBP as essential chromatin partners for YAP-driven transcription in GNAQ-mutant uveal melanoma. The work points to p300/CBP dependency as a potential therapeutic entry point for a cancer subtype with limited effective options. The screen focuses on chromatin regulation as a driver of survival and transcriptional output, tying the identified factors to YAP-linked gene programs. Mechanistically, the results connect epigenetic cofactor biology with tumor dependence. For biotech stakeholders, the immediate relevance is target tractability—p300/CBP modulation is a well-studied pharmacology area—paired with the challenge of biomarker definition around YAP activity and GNAQ mutational status. The study supports a strategy of pairing chromatin-targeted agents with molecular enrollment criteria. The data adds a clear target hypothesis for preclinical validation and translational biomarker development in uveal melanoma.