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Significance Current histone deacetylase (HDAC) inhibitors have shown mixed results in the treatment of many cancer types. Our study has demonstrated significant antitumor phenotypes resulting from targeted disruption of HDAC3 and the NCOR complex with genome engineering technology. Our findings provide compelling evidence that the HDACs and their essential interacting factors remain key cancer therapeutic targets and that the next generation of selective HDAC inhibitors may improve survival of cancer patients.

CRISPR screen identifies the NCOR/HDAC3 complex as a major suppressor of differentiation in rhabdomyosarcoma